Nutrient chapter

Butyrate

Butyrate. Species, exposure and limitations are retained in each linked claim.

90 recorded mechanisms · 14 availability situations · 9 preserved sources. Draft and verified records are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

What the sources say this nutrient does, one relationship at a time. Plain wording comes first; the technical statement follows.

Butyryl-CoA:acetate CoA-transferase activity was detected in all 38 human-fecal butyrate-producing isolates examined, supporting this terminal route to butyrate.
Bacterial butyryl-CoA:acetate-CoA transferases → Butyrate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Anaerobic human-fecal isolates; enzyme assays and gene analysis.
limitations
A defined isolate panel is not a census of every human microbiome.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
Many tested gut bacteria used acetate-linked CoA transfer to finish butyrate synthesis.
primary_references
Restricted distribution of the butyrate kinase pathway among butyrate-producing bacteria from the human colon. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15028695/ · DOI 10.1128/JB.186.7.2099-2106.2004
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 38–44
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Anaerobic human-fecal isolates; enzyme assays and gene analysis. · source_derived_draft · unverified_draft
## butyrate-coa-transferase-route Many tested gut bacteria used acetate-linked CoA transfer to finish butyrate synthesis. Butyryl-CoA:acetate CoA-transferase activity was detected in all 38 human-fecal butyrate-producing isolates examined, supporting this terminal route to butyrate. Model: Anaerobic human-fecal isolates; enzyme assays and gene analysis. Limitations: A defined isolate panel is not a census of every human microbiome. Evidence access: Primary abstract Restricted distribution of the butyrate kinase pathway among butyrate-producing bacteria from the human colon. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15028695/ · DOI 10.1128/JB.186.7.2099-2106.2004
Complete structured claim and evidence
Only four of 38 examined butyrate-producing isolates had detectable butyrate-kinase activity; the alternative terminal pathway includes phosphotransbutyrylase and butyrate kinase.
Bacterial butyrate kinases → Butyrate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human-fecal anaerobic isolates, activity assays and PCR.
limitations
Do not assign the kinase route to every producer.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
A second route existed but was less widespread in this isolate panel.
primary_references
Restricted distribution of the butyrate kinase pathway among butyrate-producing bacteria from the human colon. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15028695/ · DOI 10.1128/JB.186.7.2099-2106.2004
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 46–52
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human-fecal anaerobic isolates, activity assays and PCR. · source_derived_draft · unverified_draft
## butyrate-kinase-route A second route existed but was less widespread in this isolate panel. Only four of 38 examined butyrate-producing isolates had detectable butyrate-kinase activity; the alternative terminal pathway includes phosphotransbutyrylase and butyrate kinase. Model: Human-fecal anaerobic isolates, activity assays and PCR. Limitations: Do not assign the kinase route to every producer. Evidence access: Primary abstract Restricted distribution of the butyrate kinase pathway among butyrate-producing bacteria from the human colon. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15028695/ · DOI 10.1128/JB.186.7.2099-2106.2004
Complete structured claim and evidence
Isotope tracing showed external acetate supplied 85–90% of butyrate carbon in the tested F. prausnitzii and Roseburia cultures supplied with 60 mM acetate and 10 mM glucose.
Acetate → Butyrate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human-fecal bacterial isolates and 13C-acetate tracing.
limitations
This culture fraction is not a universal human conversion percentage.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
One bacterium’s fermentation product can become another product’s carbon source.
primary_references
Contribution of acetate to butyrate formation by human faecal bacteria. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15182395/ · DOI 10.1079/BJN20041150
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 54–60
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human-fecal bacterial isolates and 13C-acetate tracing. · source_derived_draft · unverified_draft
## butyrate-acetate-carbon One bacterium’s fermentation product can become another product’s carbon source. Isotope tracing showed external acetate supplied 85–90% of butyrate carbon in the tested F. prausnitzii and Roseburia cultures supplied with 60 mM acetate and 10 mM glucose. Model: Human-fecal bacterial isolates and 13C-acetate tracing. Limitations: This culture fraction is not a universal human conversion percentage. Evidence access: Primary abstract Contribution of acetate to butyrate formation by human faecal bacteria. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15182395/ · DOI 10.1079/BJN20041150
Complete structured claim and evidence
E. hallii-related and A. caccae isolates consumed lactate and formed butyrate; coculture with starch-utilizing B. adolescentis removed detectable L-lactate and generated butyrate.
L-Lactate → Butyrate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human-fecal isolates and defined cocultures.
limitations
Strain-specific capacity; several other butyrate-producing species did not use lactate.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
Cooperating bacteria turned lactate from starch fermentation into butyrate.
primary_references
Lactate-utilizing bacteria, isolated from human feces, that produce butyrate as a major fermentation product. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15466518/ · DOI 10.1128/AEM.70.10.5810-5817.2004
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 62–68
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human-fecal isolates and defined cocultures. · source_derived_draft · unverified_draft
## butyrate-lactate-crossfeeding Cooperating bacteria turned lactate from starch fermentation into butyrate. E. hallii-related and A. caccae isolates consumed lactate and formed butyrate; coculture with starch-utilizing B. adolescentis removed detectable L-lactate and generated butyrate. Model: Human-fecal isolates and defined cocultures. Limitations: Strain-specific capacity; several other butyrate-producing species did not use lactate. Evidence access: Primary abstract Lactate-utilizing bacteria, isolated from human feces, that produce butyrate as a major fermentation product. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15466518/ · DOI 10.1128/AEM.70.10.5810-5817.2004
Complete structured claim and evidence
Adding glucose prevented lactate utilization by the tested lactate-to-butyrate isolates until glucose was exhausted.
D-glucose → Gut microbial butyrate production source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Anaerobic batch cultures.
limitations
A substrate-preference experiment does not mean dietary glucose universally suppresses human butyrate production.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
The available carbohydrate changed which substrate microbes used first.
primary_references
Lactate-utilizing bacteria, isolated from human feces, that produce butyrate as a major fermentation product. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15466518/ · DOI 10.1128/AEM.70.10.5810-5817.2004
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 70–76
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Anaerobic batch cultures. · source_derived_draft · unverified_draft
## butyrate-glucose-switch The available carbohydrate changed which substrate microbes used first. Adding glucose prevented lactate utilization by the tested lactate-to-butyrate isolates until glucose was exhausted. Model: Anaerobic batch cultures. Limitations: A substrate-preference experiment does not mean dietary glucose universally suppresses human butyrate production. Evidence access: Primary abstract Lactate-utilizing bacteria, isolated from human feces, that produce butyrate as a major fermentation product. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15466518/ · DOI 10.1128/AEM.70.10.5810-5817.2004
Complete structured claim and evidence
In the 174-person two-week fiber study, resistant potato starch produced the greatest fecal SCFA/butyrate rise; resistant maize starch and inulin did not significantly increase fecal butyrate.
Resistant potato starch preparation → Human fecal butyrate concentration source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Healthy young adults; four dietary interventions.
limitations
Fecal concentration is not a direct measure of total production or absorbed dose.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
Fiber type and the starting microbial community changed the response.
primary_references
Dynamics of Human Gut Microbiota and Short-Chain Fatty Acids in Response to Dietary Interventions with Three Fermentable Fibers. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30696735/ · DOI 10.1128/mBio.02566-18
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 78–84
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Healthy young adults; four dietary interventions. · source_derived_draft · unverified_draft
## butyrate-resistant-starch-human Fiber type and the starting microbial community changed the response. In the 174-person two-week fiber study, resistant potato starch produced the greatest fecal SCFA/butyrate rise; resistant maize starch and inulin did not significantly increase fecal butyrate. Model: Healthy young adults; four dietary interventions. Limitations: Fecal concentration is not a direct measure of total production or absorbed dose. Evidence access: Primary abstract Dynamics of Human Gut Microbiota and Short-Chain Fatty Acids in Response to Dietary Interventions with Three Fermentable Fibers. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30696735/ · DOI 10.1128/mBio.02566-18
Complete structured claim and evidence
Combining the 50 and 100 mg/day riboflavin arms in RIBOGUT showed increased fecal butyrate after two weeks; separate-dose analyses showed only minor SCFA differences.
Riboflavin (vitamin B2) → Human fecal butyrate concentration source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text, results and Figure 6
experimental_model
Randomized placebo-controlled human study; pooled dose analysis.
limitations
Fecal concentration was measured, not production flux. Neither dose increased F. prausnitzii abundance; this does not establish a universal B2 deficiency gate.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
A vitamin B2 trial found a butyrate signal after pooling doses.
primary_references
Riboflavin Supplementation Promotes Butyrate Production in the Absence of Gross Compositional Changes in the Gut Microbiota. · 2023 · https://pubmed.ncbi.nlm.nih.gov/35943883/ · DOI 10.1089/ars.2022.0033
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 86–92
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Randomized placebo-controlled human study; pooled dose analysis. · source_derived_draft · unverified_draft
## butyrate-riboflavin-pooled A vitamin B2 trial found a butyrate signal after pooling doses. Combining the 50 and 100 mg/day riboflavin arms in RIBOGUT showed increased fecal butyrate after two weeks; separate-dose analyses showed only minor SCFA differences. Model: Randomized placebo-controlled human study; pooled dose analysis. Limitations: Fecal concentration was measured, not production flux. Neither dose increased F. prausnitzii abundance; this does not establish a universal B2 deficiency gate. Evidence access: Primary full text, results and Figure 6 Riboflavin Supplementation Promotes Butyrate Production in the Absence of Gross Compositional Changes in the Gut Microbiota. · 2023 · https://pubmed.ncbi.nlm.nih.gov/35943883/ · DOI 10.1089/ars.2022.0033
Complete structured claim and evidence
Colon-delivered isotope tracing in 12 healthy people estimated 24% conversion of acetate into butyrate, the largest measured SCFA interconversion.
Acetate → Butyrate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human stable-isotope colon-delivery study.
limitations
A study-specific tracer estimate, not a recommended acetate dose or a universal conversion fraction.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
Cross-feeding was detectable in humans as well as cultures.
primary_references
Systemic availability and metabolism of colonic-derived short-chain fatty acids in healthy subjects: a stable isotope study. · 2017 · https://pubmed.ncbi.nlm.nih.gov/27510655/ · DOI 10.1113/JP272613
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 94–100
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human stable-isotope colon-delivery study. · source_derived_draft · unverified_draft
## butyrate-human-acetate-conversion Cross-feeding was detectable in humans as well as cultures. Colon-delivered isotope tracing in 12 healthy people estimated 24% conversion of acetate into butyrate, the largest measured SCFA interconversion. Model: Human stable-isotope colon-delivery study. Limitations: A study-specific tracer estimate, not a recommended acetate dose or a universal conversion fraction. Evidence access: Primary abstract Systemic availability and metabolism of colonic-derived short-chain fatty acids in healthy subjects: a stable isotope study. · 2017 · https://pubmed.ncbi.nlm.nih.gov/27510655/ · DOI 10.1113/JP272613
Complete structured claim and evidence
Expressing human intestinal SLC5A8 in Xenopus oocytes increased butyrate uptake and generated sodium-dependent inward currents.
Human sodium-coupled monocarboxylate transporter 1 / SLC5A8 → Butyrate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human SLC5A8 expressed in frog oocytes; radiotracer and voltage-clamp assays.
limitations
Expression host is not the protein species. This does not establish that extra dietary sodium improves uptake.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
A human transporter can concentrate butyrate using a sodium gradient.
primary_references
Functional identification of SLC5A8, a tumor suppressor down-regulated in colon cancer, as a Na(+)-coupled transporter for short-chain fatty acids. · 2004 · https://pubmed.ncbi.nlm.nih.gov/14966140/ · DOI 10.1074/jbc.C400059200
transport_effect
raises Expression increased butyrate uptake and generated sodium-dependent inward currents.
transport_pool
the expressing cell Expression increased butyrate uptake and generated sodium-dependent inward currents.
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 102–108
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human SLC5A8 expressed in frog oocytes; radiotracer and voltage-clamp assays. · source_derived_draft · unverified_draft
## butyrate-smct1-uptake A human transporter can concentrate butyrate using a sodium gradient. Expressing human intestinal SLC5A8 in Xenopus oocytes increased butyrate uptake and generated sodium-dependent inward currents. Model: Human SLC5A8 expressed in frog oocytes; radiotracer and voltage-clamp assays. Limitations: Expression host is not the protein species. This does not establish that extra dietary sodium improves uptake. Evidence access: Primary abstract Functional identification of SLC5A8, a tumor suppressor down-regulated in colon cancer, as a Na(+)-coupled transporter for short-chain fatty acids. · 2004 · https://pubmed.ncbi.nlm.nih.gov/14966140/ · DOI 10.1074/jbc.C400059200
Complete structured claim and evidence
Human SMCT/SLC5A8 transport-associated currents depended on external sodium; chloride influenced part of the current but was not cotransported.
Sodium ion → Human SLC5A8-mediated butyrate uptake source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human transporter expressed in Xenopus oocytes.
limitations
Assay currents do not by themselves define a clinical electrolyte threshold or a universal coupling ratio for every substrate.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
Sodium dependence is different from chloride being a transported substrate.
primary_references
The human tumour suppressor gene SLC5A8 expresses a Na+-monocarboxylate cotransporter. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15090606/ · DOI 10.1113/jphysiol.2004.063859
trigger_kind
machinery_impairment Imported condition classification; unverified.
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 110–116
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human transporter expressed in Xenopus oocytes. · source_derived_draft · unverified_draft
## butyrate-smct1-sodium-loss Sodium dependence is different from chloride being a transported substrate. Human SMCT/SLC5A8 transport-associated currents depended on external sodium; chloride influenced part of the current but was not cotransported. Model: Human transporter expressed in Xenopus oocytes. Limitations: Assay currents do not by themselves define a clinical electrolyte threshold or a universal coupling ratio for every substrate. Evidence access: Primary abstract The human tumour suppressor gene SLC5A8 expresses a Na+-monocarboxylate cotransporter. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15090606/ · DOI 10.1113/jphysiol.2004.063859
Complete structured claim and evidence
Probenecid or ibuprofen at 1 mM strongly inhibited human SLC5A8 activity in the oocyte assay.
Human sodium-coupled monocarboxylate transporter 1 / SLC5A8 → Human SLC5A8-mediated butyrate uptake source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human transporter voltage-clamp experiments.
limitations
High bath concentrations do not prove clinically meaningful butyrate depletion or justify changing a medicine.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
Drugs can block this transporter under experimental conditions.
primary_references
The human tumour suppressor gene SLC5A8 expresses a Na+-monocarboxylate cotransporter. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15090606/ · DOI 10.1113/jphysiol.2004.063859
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 118–124
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human transporter voltage-clamp experiments. · source_derived_draft · unverified_draft
## butyrate-smct1-drug-block Drugs can block this transporter under experimental conditions. Probenecid or ibuprofen at 1 mM strongly inhibited human SLC5A8 activity in the oocyte assay. Model: Human transporter voltage-clamp experiments. Limitations: High bath concentrations do not prove clinically meaningful butyrate depletion or justify changing a medicine. Evidence access: Primary abstract The human tumour suppressor gene SLC5A8 expresses a Na+-monocarboxylate cotransporter. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15090606/ · DOI 10.1113/jphysiol.2004.063859
Complete structured claim and evidence
At 2 mM sodium butyrate, human AA/C1 colonic cells increased MCT1 mRNA and protein through transcription and greater mRNA stability.
Butyrate → Human monocarboxylate transporter 1 / SLC16A1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human colonic epithelial AA/C1 cultures.
limitations
Acetate and propionate did not reproduce this response; exposure and cell state matter.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
Butyrate increased the capacity of one of its own uptake routes.
primary_references
Substrate-induced regulation of the human colonic monocarboxylate transporter, MCT1. · 2002 · https://pubmed.ncbi.nlm.nih.gov/11882670/ · DOI 10.1113/jphysiol.2001.014241
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 126–132
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human colonic epithelial AA/C1 cultures. · source_derived_draft · unverified_draft
## butyrate-mct1-expression Butyrate increased the capacity of one of its own uptake routes. At 2 mM sodium butyrate, human AA/C1 colonic cells increased MCT1 mRNA and protein through transcription and greater mRNA stability. Model: Human colonic epithelial AA/C1 cultures. Limitations: Acetate and propionate did not reproduce this response; exposure and cell state matter. Evidence access: Primary abstract Substrate-induced regulation of the human colonic monocarboxylate transporter, MCT1. · 2002 · https://pubmed.ncbi.nlm.nih.gov/11882670/ · DOI 10.1113/jphysiol.2001.014241
Complete structured claim and evidence
After preincubation with 2 mM sodium butyrate, AA/C1 cells increased the maximal butyrate uptake rate about fivefold without a significant change in apparent Km.
Human monocarboxylate transporter 1 / SLC16A1 → Human colonic-cell butyrate transport source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human colonic-cell radiotracer uptake.
limitations
An adaptive culture response does not establish oral bioavailability.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
Transport capacity increased rather than measured substrate affinity.
primary_references
Substrate-induced regulation of the human colonic monocarboxylate transporter, MCT1. · 2002 · https://pubmed.ncbi.nlm.nih.gov/11882670/ · DOI 10.1113/jphysiol.2001.014241
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 134–140
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human colonic-cell radiotracer uptake. · source_derived_draft · unverified_draft
## butyrate-mct1-capacity Transport capacity increased rather than measured substrate affinity. After preincubation with 2 mM sodium butyrate, AA/C1 cells increased the maximal butyrate uptake rate about fivefold without a significant change in apparent Km. Model: Human colonic-cell radiotracer uptake. Limitations: An adaptive culture response does not establish oral bioavailability. Evidence access: Primary abstract Substrate-induced regulation of the human colonic monocarboxylate transporter, MCT1. · 2002 · https://pubmed.ncbi.nlm.nih.gov/11882670/ · DOI 10.1113/jphysiol.2001.014241
Complete structured claim and evidence
In 12 healthy subjects receiving isotope-labeled SCFAs in colon-release capsules, systemic availability was approximately 2% for butyrate, compared with 9% propionate and 36% acetate.
Butyrate → Systemic availability of colon-delivered butyrate in humans source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human stable-isotope pharmacokinetic study.
limitations
Specific to colonic delivery and study conditions; does not quantify oral immediate-release, rectal or injected exposure.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
Most colon-delivered butyrate did not reach the general circulation unchanged.
primary_references
Systemic availability and metabolism of colonic-derived short-chain fatty acids in healthy subjects: a stable isotope study. · 2017 · https://pubmed.ncbi.nlm.nih.gov/27510655/ · DOI 10.1113/JP272613
trigger_kind
biomarker_context Imported condition classification; unverified.
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 142–148
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human stable-isotope pharmacokinetic study. · source_derived_draft · unverified_draft
## butyrate-systemic-availability Most colon-delivered butyrate did not reach the general circulation unchanged. In 12 healthy subjects receiving isotope-labeled SCFAs in colon-release capsules, systemic availability was approximately 2% for butyrate, compared with 9% propionate and 36% acetate. Model: Human stable-isotope pharmacokinetic study. Limitations: Specific to colonic delivery and study conditions; does not quantify oral immediate-release, rectal or injected exposure. Evidence access: Primary abstract Systemic availability and metabolism of colonic-derived short-chain fatty acids in healthy subjects: a stable isotope study. · 2017 · https://pubmed.ncbi.nlm.nih.gov/27510655/ · DOI 10.1113/JP272613
Complete structured claim and evidence
Butyrate increased apical NHE3 protein and sodium/hydrogen exchange activity in human C2/bbe monolayers, while NHE2 did not increase.
Butyrate → Human sodium/hydrogen exchanger 3 / SLC9A3 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human colonic-cell exposure experiments.
limitations
The separate pectin-fed rat arm is not an isolated human butyrate intervention or proof of net whole-body sodium retention.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
It changed machinery that supports intestinal sodium absorption.
primary_references
SCFA increase intestinal Na absorption by induction of NHE3 in rat colon and human intestinal C2/bbe cells. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11254495/ · DOI 10.1152/ajpgi.2001.280.4.G687
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AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human colonic-cell exposure experiments. · source_derived_draft · unverified_draft
## butyrate-nhe3-sodium It changed machinery that supports intestinal sodium absorption. Butyrate increased apical NHE3 protein and sodium/hydrogen exchange activity in human C2/bbe monolayers, while NHE2 did not increase. Model: Human colonic-cell exposure experiments. Limitations: The separate pectin-fed rat arm is not an isolated human butyrate intervention or proof of net whole-body sodium retention. Evidence access: Primary abstract SCFA increase intestinal Na absorption by induction of NHE3 in rat colon and human intestinal C2/bbe cells. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11254495/ · DOI 10.1152/ajpgi.2001.280.4.G687
Complete structured claim and evidence
Tributyrin administration replenished colonic butyrate and HIF-related responses in antibiotic-treated mice in the PHD study.
Tributyrin / glycerol tributyrate → Butyrate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text, Figure 5
experimental_model
Antibiotic-treated mice; tributyrin reconstitution.
limitations
Tributyrin and free sodium butyrate are different preparations; this does not establish equal release sites or human doses.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
A glycerol ester supplied butyrate in the depletion experiment.
primary_references
Microbiota-derived butyrate is an endogenous HIF prolyl hydroxylase inhibitor. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34190032/ · DOI 10.1080/19490976.2021.1938380
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 158–164
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Antibiotic-treated mice; tributyrin reconstitution. · source_derived_draft · unverified_draft
## butyrate-tributyrin-repletion A glycerol ester supplied butyrate in the depletion experiment. Tributyrin administration replenished colonic butyrate and HIF-related responses in antibiotic-treated mice in the PHD study. Model: Antibiotic-treated mice; tributyrin reconstitution. Limitations: Tributyrin and free sodium butyrate are different preparations; this does not establish equal release sites or human doses. Evidence access: Primary full text, Figure 5 Microbiota-derived butyrate is an endogenous HIF prolyl hydroxylase inhibitor. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34190032/ · DOI 10.1080/19490976.2021.1938380
Complete structured claim and evidence
Germ-free mouse colonocytes had reduced NADH/NAD+, oxidative phosphorylation and ATP; adding butyrate rescued mitochondrial respiration.
Butyrate → Mouse colonocyte mitochondrial respiration and energy state source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Germ-free mouse colonocytes and ex-vivo substrate addition.
limitations
Germ-free status removes many microbial functions; rescue supports a butyrate contribution without making every change a specific deficiency effect.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
Removing the microbiota deprived colon cells of an important fuel; adding it back restored respiration.
primary_references
The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21531334/ · DOI 10.1016/j.cmet.2011.02.018
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 166–172
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Germ-free mouse colonocytes and ex-vivo substrate addition. · source_derived_draft · unverified_draft
## butyrate-germfree-energy Removing the microbiota deprived colon cells of an important fuel; adding it back restored respiration. Germ-free mouse colonocytes had reduced NADH/NAD+, oxidative phosphorylation and ATP; adding butyrate rescued mitochondrial respiration. Model: Germ-free mouse colonocytes and ex-vivo substrate addition. Limitations: Germ-free status removes many microbial functions; rescue supports a butyrate contribution without making every change a specific deficiency effect. Evidence access: Primary abstract The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21531334/ · DOI 10.1016/j.cmet.2011.02.018
Complete structured claim and evidence
Butyrate addition prevented energy-stress-associated autophagy in germ-free mouse colonocytes, with fuel use rather than HDAC inhibition explaining the rescue.
Butyrate → Mouse colonocyte autophagy during microbial metabolite depletion source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Mouse colonocyte substrate-rescue experiments.
limitations
Autophagy is a context-dependent response, not universally harmful.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
Supplying energy reduced the need for the cell’s recycling response.
primary_references
The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21531334/ · DOI 10.1016/j.cmet.2011.02.018
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 174–180
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse colonocyte substrate-rescue experiments. · source_derived_draft · unverified_draft
## butyrate-autophagy-rescue Supplying energy reduced the need for the cell’s recycling response. Butyrate addition prevented energy-stress-associated autophagy in germ-free mouse colonocytes, with fuel use rather than HDAC inhibition explaining the rescue. Model: Mouse colonocyte substrate-rescue experiments. Limitations: Autophagy is a context-dependent response, not universally harmful. Evidence access: Primary abstract The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21531334/ · DOI 10.1016/j.cmet.2011.02.018
Complete structured claim and evidence
In the colonic-cell experiments, butyrate metabolism supplied acetyl-CoA for energy metabolism and histone acetyltransferase activity.
Butyrate → Acetyl-CoA source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human colonic-cell metabolic experiments.
limitations
This is a multistep metabolic conversion; no single CoA ligase is assigned without direct evidence.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
The same carbon source supported both fuel use and adding acetyl marks.
primary_references
The Warburg effect dictates the mechanism of butyrate-mediated histone acetylation and cell proliferation. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23063526/ · DOI 10.1016/j.molcel.2012.08.033
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 182–188
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human colonic-cell metabolic experiments. · source_derived_draft · unverified_draft
## butyrate-acetyl-coa The same carbon source supported both fuel use and adding acetyl marks. In the colonic-cell experiments, butyrate metabolism supplied acetyl-CoA for energy metabolism and histone acetyltransferase activity. Model: Human colonic-cell metabolic experiments. Limitations: This is a multistep metabolic conversion; no single CoA ligase is assigned without direct evidence. Evidence access: Primary abstract The Warburg effect dictates the mechanism of butyrate-mediated histone acetylation and cell proliferation. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23063526/ · DOI 10.1016/j.molcel.2012.08.033
Complete structured claim and evidence
In glycolysis-dominant cancerous colonocytes, reduced butyrate utilization allowed accumulation and HDAC inhibition; altering the metabolic state changed the response.
Butyrate → Human colonic-cell HDAC activity in butyrate experiments; isoforms unresolved source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human colonic-cell comparisons and metabolic manipulation.
limitations
A cell-state mechanism is not proof that all tumors respond alike or that dietary butyrate treats cancer.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
How the cell burns fuel changed how strongly butyrate affected gene regulation.
primary_references
The Warburg effect dictates the mechanism of butyrate-mediated histone acetylation and cell proliferation. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23063526/ · DOI 10.1016/j.molcel.2012.08.033
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 190–196
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human colonic-cell comparisons and metabolic manipulation. · source_derived_draft · unverified_draft
## butyrate-warburg-hdac How the cell burns fuel changed how strongly butyrate affected gene regulation. In glycolysis-dominant cancerous colonocytes, reduced butyrate utilization allowed accumulation and HDAC inhibition; altering the metabolic state changed the response. Model: Human colonic-cell comparisons and metabolic manipulation. Limitations: A cell-state mechanism is not proof that all tumors respond alike or that dietary butyrate treats cancer. Evidence access: Primary abstract The Warburg effect dictates the mechanism of butyrate-mediated histone acetylation and cell proliferation. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23063526/ · DOI 10.1016/j.molcel.2012.08.033
Complete structured claim and evidence
Butyrate stimulated proliferation in the tested oxidative settings but inhibited proliferation in cells undergoing the Warburg effect.
Butyrate → Metabolism-dependent proliferation response to butyrate in human colonic cells source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human noncancerous and cancerous colonic-cell experiments.
limitations
This is an experimentally explained context difference, not a draft correction or an unexplained universal contradiction.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
One molecule produced opposite growth responses in different metabolic states.
primary_references
The Warburg effect dictates the mechanism of butyrate-mediated histone acetylation and cell proliferation. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23063526/ · DOI 10.1016/j.molcel.2012.08.033
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 198–204
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human noncancerous and cancerous colonic-cell experiments. · source_derived_draft · unverified_draft
## butyrate-warburg-growth One molecule produced opposite growth responses in different metabolic states. Butyrate stimulated proliferation in the tested oxidative settings but inhibited proliferation in cells undergoing the Warburg effect. Model: Human noncancerous and cancerous colonic-cell experiments. Limitations: This is an experimentally explained context difference, not a draft correction or an unexplained universal contradiction. Evidence access: Primary abstract The Warburg effect dictates the mechanism of butyrate-mediated histone acetylation and cell proliferation. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23063526/ · DOI 10.1016/j.molcel.2012.08.033
Complete structured claim and evidence
Acads-deficient colonocytes oxidized less butyrate; knockout mice had a smaller crypt proliferative zone that exogenous butyrate further suppressed.
Mouse short-chain acyl-CoA dehydrogenase / Acads → Mouse colonocyte butyrate oxidation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text, Figure 6
experimental_model
Mouse Acads knockout, colonocyte metabolism and crypt measurements.
limitations
ACADS participates in oxidation; it does not perform the entire butyrate-to-acetyl-CoA pathway alone. Correction record: A published erratum is confirmed by PubMed and publisher/Crossref metadata: Cell 167(4):1137, 2016. The notice body was not available through the accessed publisher endpoints. The main article's Acads/Foxo3 and crypt experiments were read, but the specific effect of the correction remains unassessed. https://pubmed.ncbi.nlm.nih.gov/27814510/
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
Weakening fuel oxidation let butyrate affect cells normally protected from it.
primary_references
The Colonic Crypt Protects Stem Cells from Microbiota-Derived Metabolites. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27264604/ · DOI 10.1016/j.cell.2016.05.018
trigger_kind
machinery_impairment Imported condition classification; unverified.
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 206–212
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse Acads knockout, colonocyte metabolism and crypt measurements. · source_derived_draft · unverified_draft
## butyrate-acads-loss Weakening fuel oxidation let butyrate affect cells normally protected from it. Acads-deficient colonocytes oxidized less butyrate; knockout mice had a smaller crypt proliferative zone that exogenous butyrate further suppressed. Model: Mouse Acads knockout, colonocyte metabolism and crypt measurements. Limitations: ACADS participates in oxidation; it does not perform the entire butyrate-to-acetyl-CoA pathway alone. Correction record: A published erratum is confirmed by PubMed and publisher/Crossref metadata: Cell 167(4):1137, 2016. The notice body was not available through the accessed publisher endpoints. The main article's Acads/Foxo3 and crypt experiments were read, but the specific effect of the correction remains unassessed. https://pubmed.ncbi.nlm.nih.gov/27814510/ Evidence access: Primary full text, Figure 6 The Colonic Crypt Protects Stem Cells from Microbiota-Derived Metabolites. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27264604/ · DOI 10.1016/j.cell.2016.05.018
Complete structured claim and evidence
Microbiota-supported PPAR-gamma signaling drove mouse colonocytes toward beta-oxidation, limiting oxygen available to bacteria in the colonic lumen.
Butyrate → Mouse colonic epithelial oxygen consumption source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mouse antibiotic, epithelial Pparg and microbial respiration experiments.
limitations
Pathway dependence does not establish direct binding of butyrate to PPAR-gamma.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
Colon-cell fuel use helped keep the neighboring microbial environment low in oxygen.
primary_references
Microbiota-activated PPAR-γ signaling inhibits dysbiotic Enterobacteriaceae expansion. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28798125/ · DOI 10.1126/science.aam9949
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 214–220
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse antibiotic, epithelial Pparg and microbial respiration experiments. · source_derived_draft · unverified_draft
## butyrate-pparg-oxygen Colon-cell fuel use helped keep the neighboring microbial environment low in oxygen. Microbiota-supported PPAR-gamma signaling drove mouse colonocytes toward beta-oxidation, limiting oxygen available to bacteria in the colonic lumen. Model: Mouse antibiotic, epithelial Pparg and microbial respiration experiments. Limitations: Pathway dependence does not establish direct binding of butyrate to PPAR-gamma. Evidence access: Primary abstract Microbiota-activated PPAR-γ signaling inhibits dysbiotic Enterobacteriaceae expansion. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28798125/ · DOI 10.1126/science.aam9949
Complete structured claim and evidence
Loss of epithelial PPAR-gamma signaling increased Nos2 expression and colonic nitrate availability in the mouse study.
Mouse peroxisome proliferator-activated receptor gamma / Pparg → Mouse inducible nitric oxide synthase / Nos2 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Mouse epithelial signaling and luminal metabolite experiments.
limitations
Nitrate is a downstream electron acceptor; butyrate is not being claimed to chemically remove nitrate.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
Changing host signaling supplied a different bacterial respiratory fuel.
primary_references
Microbiota-activated PPAR-γ signaling inhibits dysbiotic Enterobacteriaceae expansion. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28798125/ · DOI 10.1126/science.aam9949
trigger_kind
machinery_impairment Imported condition classification; unverified.
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 222–228
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse epithelial signaling and luminal metabolite experiments. · source_derived_draft · unverified_draft
## butyrate-pparg-nos2 Changing host signaling supplied a different bacterial respiratory fuel. Loss of epithelial PPAR-gamma signaling increased Nos2 expression and colonic nitrate availability in the mouse study. Model: Mouse epithelial signaling and luminal metabolite experiments. Limitations: Nitrate is a downstream electron acceptor; butyrate is not being claimed to chemically remove nitrate. Evidence access: Primary abstract Microbiota-activated PPAR-γ signaling inhibits dysbiotic Enterobacteriaceae expansion. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28798125/ · DOI 10.1126/science.aam9949
Complete structured claim and evidence
The mouse experiments linked increased luminal respiratory electron acceptors to expansion of Escherichia and Salmonella when the PPAR-gamma homeostatic pathway was disrupted.
Mouse colonic luminal nitrate availability → Mouse colonic Enterobacteriaceae expansion source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mouse microbiota perturbation and bacterial respiration experiments.
limitations
The pathway is not a universal explanation for every case of dysbiosis.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
Host metabolism changed which bacteria could expand.
primary_references
Microbiota-activated PPAR-γ signaling inhibits dysbiotic Enterobacteriaceae expansion. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28798125/ · DOI 10.1126/science.aam9949
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 230–236
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse microbiota perturbation and bacterial respiration experiments. · source_derived_draft · unverified_draft
## butyrate-electron-acceptor-growth Host metabolism changed which bacteria could expand. The mouse experiments linked increased luminal respiratory electron acceptors to expansion of Escherichia and Salmonella when the PPAR-gamma homeostatic pathway was disrupted. Model: Mouse microbiota perturbation and bacterial respiration experiments. Limitations: The pathway is not a universal explanation for every case of dysbiosis. Evidence access: Primary abstract Microbiota-activated PPAR-γ signaling inhibits dysbiotic Enterobacteriaceae expansion. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28798125/ · DOI 10.1126/science.aam9949
Complete structured claim and evidence
Butyrate increased epithelial oxygen consumption and stabilized HIF in intestinal epithelial-cell experiments.
Butyrate → HIF stabilization in butyrate-exposed human epithelial cells source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human intestinal epithelial cultures, with separate mouse depletion/repletion experiments.
limitations
HIF stabilization has more than one possible route; this result does not exclude direct hydroxylase inhibition.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
Using the fuel changed local oxygen sensing.
primary_references
Crosstalk between Microbiota-Derived Short-Chain Fatty Acids and Intestinal Epithelial HIF Augments Tissue Barrier Function. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25865369/ · DOI 10.1016/j.chom.2015.03.005
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 238–244
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human intestinal epithelial cultures, with separate mouse depletion/repletion experiments. · source_derived_draft · unverified_draft
## butyrate-oxygen-hif Using the fuel changed local oxygen sensing. Butyrate increased epithelial oxygen consumption and stabilized HIF in intestinal epithelial-cell experiments. Model: Human intestinal epithelial cultures, with separate mouse depletion/repletion experiments. Limitations: HIF stabilization has more than one possible route; this result does not exclude direct hydroxylase inhibition. Evidence access: Primary abstract Crosstalk between Microbiota-Derived Short-Chain Fatty Acids and Intestinal Epithelial HIF Augments Tissue Barrier Function. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25865369/ · DOI 10.1016/j.chom.2015.03.005
Complete structured claim and evidence
Butyrate bound and inhibited a recombinant human PHD2 catalytic fragment; kinetic analysis gave a noncompetitive Ki of 5.3 ± 0.5 mM relative to 2-oxoglutarate.
Butyrate → EGLN1 / PHD2 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text, recombinant methods and enzyme kinetics
experimental_model
Human PHD2 residues 181–402; NMR and enzymatic assays.
limitations
Millimolar assay exposure is relevant to local gut questions, not evidence of inhibition throughout the body at normal blood levels.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
It also directly affected an enzyme that normally marks HIF for degradation.
primary_references
Microbiota-derived butyrate is an endogenous HIF prolyl hydroxylase inhibitor. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34190032/ · DOI 10.1080/19490976.2021.1938380
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 246–252
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human PHD2 residues 181–402; NMR and enzymatic assays. · source_derived_draft · unverified_draft
## butyrate-phd2-inhibition It also directly affected an enzyme that normally marks HIF for degradation. Butyrate bound and inhibited a recombinant human PHD2 catalytic fragment; kinetic analysis gave a noncompetitive Ki of 5.3 ± 0.5 mM relative to 2-oxoglutarate. Model: Human PHD2 residues 181–402; NMR and enzymatic assays. Limitations: Millimolar assay exposure is relevant to local gut questions, not evidence of inhibition throughout the body at normal blood levels. Evidence access: Primary full text, recombinant methods and enzyme kinetics Microbiota-derived butyrate is an endogenous HIF prolyl hydroxylase inhibitor. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34190032/ · DOI 10.1080/19490976.2021.1938380
Complete structured claim and evidence
Butyrate still stabilized HIF in human epithelial-cell experiments when its beta-oxidation and associated oxygen consumption were inhibited.
Butyrate → HIF stabilization in butyrate-exposed human epithelial cells source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human cell experiments with beta-oxidation inhibition.
limitations
Pharmacological inhibition has limitations; the complementary purified-PHD2 assay supports a separate mechanism.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
Fuel burning was not the only way it influenced HIF.
primary_references
Microbiota-derived butyrate is an endogenous HIF prolyl hydroxylase inhibitor. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34190032/ · DOI 10.1080/19490976.2021.1938380
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 254–260
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human cell experiments with beta-oxidation inhibition. · source_derived_draft · unverified_draft
## butyrate-hif-without-oxidation Fuel burning was not the only way it influenced HIF. Butyrate still stabilized HIF in human epithelial-cell experiments when its beta-oxidation and associated oxygen consumption were inhibited. Model: Human cell experiments with beta-oxidation inhibition. Limitations: Pharmacological inhibition has limitations; the complementary purified-PHD2 assay supports a separate mechanism. Evidence access: Primary abstract Microbiota-derived butyrate is an endogenous HIF prolyl hydroxylase inhibitor. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34190032/ · DOI 10.1080/19490976.2021.1938380
Complete structured claim and evidence
Butyrate increased AMPK activity and accelerated tight-junction assembly in human Caco-2 monolayers; compound C abolished the improvement in electrical resistance.
Butyrate → Human Caco-2 tight-junction assembly after butyrate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human Caco-2 monolayers; calcium-switch and permeability assays.
limitations
Compound C is not uniquely specific for AMPK; this is a culture mechanism, not proven treatment of human intestinal permeability.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
An energy-sensing pathway contributed to barrier assembly.
primary_references
Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19625695/ · DOI 10.3945/jn.109.104638
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 262–268
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human Caco-2 monolayers; calcium-switch and permeability assays. · source_derived_draft · unverified_draft
## butyrate-tight-junction-ampk An energy-sensing pathway contributed to barrier assembly. Butyrate increased AMPK activity and accelerated tight-junction assembly in human Caco-2 monolayers; compound C abolished the improvement in electrical resistance. Model: Human Caco-2 monolayers; calcium-switch and permeability assays. Limitations: Compound C is not uniquely specific for AMPK; this is a culture mechanism, not proven treatment of human intestinal permeability. Evidence access: Primary abstract Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19625695/ · DOI 10.3945/jn.109.104638
Complete structured claim and evidence
Sodium butyrate promoted store-operated calcium entry and activated the CaMKK-beta/AMPK pathway during Caco-2 tight-junction reassembly, without the change being explained by ATP concentration.
Butyrate → Store-operated calcium entry in butyrate-exposed Caco-2 cells source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human Caco-2 calcium-switch model.
limitations
This does not show that dietary calcium or magnesium supplementation improves the response.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
Calcium signaling helped connect butyrate to barrier repair.
primary_references
Sodium Butyrate Promotes Reassembly of Tight Junctions in Caco-2 Monolayers Involving Inhibition of MLCK/MLC2 Pathway and Phosphorylation of PKCβ2. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27735862/ · DOI 10.3390/ijms17101696
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 270–276
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human Caco-2 calcium-switch model. · source_derived_draft · unverified_draft
## butyrate-calcium-soce Calcium signaling helped connect butyrate to barrier repair. Sodium butyrate promoted store-operated calcium entry and activated the CaMKK-beta/AMPK pathway during Caco-2 tight-junction reassembly, without the change being explained by ATP concentration. Model: Human Caco-2 calcium-switch model. Limitations: This does not show that dietary calcium or magnesium supplementation improves the response. Evidence access: Primary abstract Sodium Butyrate Promotes Reassembly of Tight Junctions in Caco-2 Monolayers Involving Inhibition of MLCK/MLC2 Pathway and Phosphorylation of PKCβ2. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27735862/ · DOI 10.3390/ijms17101696
Complete structured claim and evidence
Sodium butyrate increased PKC-beta2 Ser660 phosphorylation; PKC-beta inhibition blocked the promoted junction reassembly.
Butyrate → Human protein kinase C beta II / PRKCB beta2 isoform source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human Caco-2 signaling and inhibitor experiments.
limitations
Inhibitor sensitivity does not imply direct binding of butyrate to PKC-beta2.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
A downstream kinase contributed to rebuilding the junction.
primary_references
Sodium Butyrate Promotes Reassembly of Tight Junctions in Caco-2 Monolayers Involving Inhibition of MLCK/MLC2 Pathway and Phosphorylation of PKCβ2. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27735862/ · DOI 10.3390/ijms17101696
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 278–284
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human Caco-2 signaling and inhibitor experiments. · source_derived_draft · unverified_draft
## butyrate-pkcb-junction A downstream kinase contributed to rebuilding the junction. Sodium butyrate increased PKC-beta2 Ser660 phosphorylation; PKC-beta inhibition blocked the promoted junction reassembly. Model: Human Caco-2 signaling and inhibitor experiments. Limitations: Inhibitor sensitivity does not imply direct binding of butyrate to PKC-beta2. Evidence access: Primary abstract Sodium Butyrate Promotes Reassembly of Tight Junctions in Caco-2 Monolayers Involving Inhibition of MLCK/MLC2 Pathway and Phosphorylation of PKCβ2. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27735862/ · DOI 10.3390/ijms17101696
Complete structured claim and evidence
Sodium butyrate reduced MLC2 Ser19 phosphorylation during Caco-2 tight-junction reassembly.
Butyrate → MLC2 Ser19 phosphorylation in butyrate-exposed Caco-2 cells source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human Caco-2 phosphorylation measurements.
limitations
MLC2 assay identity is retained without guessing the gene isoform from its shorthand name.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
The contractile machinery at the cell boundary changed as junctions reformed.
primary_references
Sodium Butyrate Promotes Reassembly of Tight Junctions in Caco-2 Monolayers Involving Inhibition of MLCK/MLC2 Pathway and Phosphorylation of PKCβ2. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27735862/ · DOI 10.3390/ijms17101696
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 286–292
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human Caco-2 phosphorylation measurements. · source_derived_draft · unverified_draft
## butyrate-mlc2-junction The contractile machinery at the cell boundary changed as junctions reformed. Sodium butyrate reduced MLC2 Ser19 phosphorylation during Caco-2 tight-junction reassembly. Model: Human Caco-2 phosphorylation measurements. Limitations: MLC2 assay identity is retained without guessing the gene isoform from its shorthand name. Evidence access: Primary abstract Sodium Butyrate Promotes Reassembly of Tight Junctions in Caco-2 Monolayers Involving Inhibition of MLCK/MLC2 Pathway and Phosphorylation of PKCβ2. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27735862/ · DOI 10.3390/ijms17101696
Complete structured claim and evidence
AMPK siRNA or compound C removed the barrier protection from SCFA pretreatment, including 2 mM butyrate, against ethanol in Caco-2 cells.
Human AMP-activated protein kinase complexes → Barrier function in butyrate-exposed human epithelial monolayers source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human Caco-2 cells; 40 mM ethanol challenge and AMPK perturbation.
limitations
Not evidence that butyrate makes alcohol exposure safe; AMPK subunit identity is not inferred from the accessed abstract.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
Reducing the signaling machinery removed the protective response.
primary_references
Short-chain fatty acids activate AMP-activated protein kinase and ameliorate ethanol-induced intestinal barrier dysfunction in Caco-2 cell monolayers. · 2013 · https://pubmed.ncbi.nlm.nih.gov/24132573/ · DOI 10.3945/jn.113.179549
trigger_kind
machinery_impairment Imported condition classification; unverified.
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 294–300
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human Caco-2 cells; 40 mM ethanol challenge and AMPK perturbation. · source_derived_draft · unverified_draft
## butyrate-ampk-knockdown Reducing the signaling machinery removed the protective response. AMPK siRNA or compound C removed the barrier protection from SCFA pretreatment, including 2 mM butyrate, against ethanol in Caco-2 cells. Model: Human Caco-2 cells; 40 mM ethanol challenge and AMPK perturbation. Limitations: Not evidence that butyrate makes alcohol exposure safe; AMPK subunit identity is not inferred from the accessed abstract. Evidence access: Primary abstract Short-chain fatty acids activate AMP-activated protein kinase and ameliorate ethanol-induced intestinal barrier dysfunction in Caco-2 cell monolayers. · 2013 · https://pubmed.ncbi.nlm.nih.gov/24132573/ · DOI 10.3945/jn.113.179549
Complete structured claim and evidence
Butyrate inhibited histone decrotonylation in the study linking class-I HDAC activity to crotonylation; separate mouse microbiota depletion altered colonic crotonyl marks.
Butyrate → Histone crotonylation in human cell and biochemical assays source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract and full-text HCT116/HDAC assay results
experimental_model
Human cell/biochemical assays and separately analyzed mouse colon.
limitations
Crotonylation is a distinct modification from acetylation, butyrylation and beta-hydroxybutyrylation.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
Its epigenetic effects extended beyond acetylation.
primary_references
Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29317660/ · DOI 10.1038/s41467-017-02651-5
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 302–308
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human cell/biochemical assays and separately analyzed mouse colon. · source_derived_draft · unverified_draft
## butyrate-decrotonylation Its epigenetic effects extended beyond acetylation. Butyrate inhibited histone decrotonylation in the study linking class-I HDAC activity to crotonylation; separate mouse microbiota depletion altered colonic crotonyl marks. Model: Human cell/biochemical assays and separately analyzed mouse colon. Limitations: Crotonylation is a distinct modification from acetylation, butyrylation and beta-hydroxybutyrylation. Evidence access: Primary abstract and full-text HCT116/HDAC assay results Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29317660/ · DOI 10.1038/s41467-017-02651-5
Complete structured claim and evidence
Direct butyrate exposure suppressed mouse colonic stem/progenitor-cell proliferation; mature colonocytes normally consumed butyrate and limited its access to the crypt base.
Butyrate → Mouse colonic stem/progenitor-cell proliferation source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mouse stem-cell culture, crypt architecture and injury experiments.
limitations
Anatomical access matters; this does not mean butyrate uniformly damages the intact colon. Correction record: A published erratum is confirmed by PubMed and publisher/Crossref metadata: Cell 167(4):1137, 2016. The notice body was not available through the accessed publisher endpoints. The main article's Acads/Foxo3 and crypt experiments were read, but the specific effect of the correction remains unassessed. https://pubmed.ncbi.nlm.nih.gov/27814510/
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
The normal tissue layout protected dividing cells from excessive local exposure.
primary_references
The Colonic Crypt Protects Stem Cells from Microbiota-Derived Metabolites. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27264604/ · DOI 10.1016/j.cell.2016.05.018
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 310–316
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse stem-cell culture, crypt architecture and injury experiments. · source_derived_draft · unverified_draft
## butyrate-crypt-exposure The normal tissue layout protected dividing cells from excessive local exposure. Direct butyrate exposure suppressed mouse colonic stem/progenitor-cell proliferation; mature colonocytes normally consumed butyrate and limited its access to the crypt base. Model: Mouse stem-cell culture, crypt architecture and injury experiments. Limitations: Anatomical access matters; this does not mean butyrate uniformly damages the intact colon. Correction record: A published erratum is confirmed by PubMed and publisher/Crossref metadata: Cell 167(4):1137, 2016. The notice body was not available through the accessed publisher endpoints. The main article's Acads/Foxo3 and crypt experiments were read, but the specific effect of the correction remains unassessed. https://pubmed.ncbi.nlm.nih.gov/27814510/ Evidence access: Primary abstract The Colonic Crypt Protects Stem Cells from Microbiota-Derived Metabolites. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27264604/ · DOI 10.1016/j.cell.2016.05.018
Complete structured claim and evidence
When mucosal injury exposed proliferating crypt cells to butyrate, epithelial proliferation and wound repair were delayed in the mouse experiments.
Butyrate → Mouse colonic epithelial wound repair source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mouse mucosal injury and local butyrate exposure.
limitations
This model does not establish the clinical effect of oral butyrate in every inflammatory bowel condition. Correction record: A published erratum is confirmed by PubMed and publisher/Crossref metadata: Cell 167(4):1137, 2016. The notice body was not available through the accessed publisher endpoints. The main article's Acads/Foxo3 and crypt experiments were read, but the specific effect of the correction remains unassessed. https://pubmed.ncbi.nlm.nih.gov/27814510/
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
Loss of the protective layer changed the response during repair.
primary_references
The Colonic Crypt Protects Stem Cells from Microbiota-Derived Metabolites. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27264604/ · DOI 10.1016/j.cell.2016.05.018
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 318–324
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse mucosal injury and local butyrate exposure. · source_derived_draft · unverified_draft
## butyrate-wound-delay Loss of the protective layer changed the response during repair. When mucosal injury exposed proliferating crypt cells to butyrate, epithelial proliferation and wound repair were delayed in the mouse experiments. Model: Mouse mucosal injury and local butyrate exposure. Limitations: This model does not establish the clinical effect of oral butyrate in every inflammatory bowel condition. Correction record: A published erratum is confirmed by PubMed and publisher/Crossref metadata: Cell 167(4):1137, 2016. The notice body was not available through the accessed publisher endpoints. The main article's Acads/Foxo3 and crypt experiments were read, but the specific effect of the correction remains unassessed. https://pubmed.ncbi.nlm.nih.gov/27814510/ Evidence access: Primary abstract The Colonic Crypt Protects Stem Cells from Microbiota-Derived Metabolites. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27264604/ · DOI 10.1016/j.cell.2016.05.018
Complete structured claim and evidence
Foxo3 deletion, unlike Foxo1 deletion, made mouse stem/progenitor cells resistant to butyrate-mediated proliferation suppression.
Mouse forkhead transcription factor Foxo3 → Mouse colonic stem/progenitor-cell proliferation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text, Figure 7
experimental_model
Mouse genetic stem-cell experiments.
limitations
Loss of a response is not rescue of a nutrient deficiency. Correction record: A published erratum is confirmed by PubMed and publisher/Crossref metadata: Cell 167(4):1137, 2016. The notice body was not available through the accessed publisher endpoints. The main article's Acads/Foxo3 and crypt experiments were read, but the specific effect of the correction remains unassessed. https://pubmed.ncbi.nlm.nih.gov/27814510/
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
The growth-suppressing response depended on a specific transcription factor.
primary_references
The Colonic Crypt Protects Stem Cells from Microbiota-Derived Metabolites. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27264604/ · DOI 10.1016/j.cell.2016.05.018
trigger_kind
machinery_impairment Imported condition classification; unverified.
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 326–332
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse genetic stem-cell experiments. · source_derived_draft · unverified_draft
## butyrate-foxo3-loss The growth-suppressing response depended on a specific transcription factor. Foxo3 deletion, unlike Foxo1 deletion, made mouse stem/progenitor cells resistant to butyrate-mediated proliferation suppression. Model: Mouse genetic stem-cell experiments. Limitations: Loss of a response is not rescue of a nutrient deficiency. Correction record: A published erratum is confirmed by PubMed and publisher/Crossref metadata: Cell 167(4):1137, 2016. The notice body was not available through the accessed publisher endpoints. The main article's Acads/Foxo3 and crypt experiments were read, but the specific effect of the correction remains unassessed. https://pubmed.ncbi.nlm.nih.gov/27814510/ Evidence access: Primary full text, Figure 7 The Colonic Crypt Protects Stem Cells from Microbiota-Derived Metabolites. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27264604/ · DOI 10.1016/j.cell.2016.05.018
Complete structured claim and evidence
Butyrate increased histone H3 acetylation at Foxp3 regulatory regions under Treg-polarizing conditions and promoted Treg differentiation.
Butyrate → Mouse regulatory T-cell transcription factor Foxp3 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mouse naive T-cell differentiation, chromatin measurements and colitis experiments.
limitations
Not a claim that butyrate turns every T cell into a Treg or universally suppresses immunity. Correction record: Publisher correction reviewed: Figure 1d upper-right axis identifies Neuropilin-1-positive Foxp3-positive cells; the originally printed negative-marker label was wrong. The notice does not amend the Foxp3 histone-acetylation result cited here. https://www.nature.com/articles/nature13041
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
The surrounding immune signals helped determine which gene program turned on.
primary_references
Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. · 2013 · https://pubmed.ncbi.nlm.nih.gov/24226770/ · DOI 10.1038/nature12721
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 334–340
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse naive T-cell differentiation, chromatin measurements and colitis experiments. · source_derived_draft · unverified_draft
## butyrate-foxp3-acetylation The surrounding immune signals helped determine which gene program turned on. Butyrate increased histone H3 acetylation at Foxp3 regulatory regions under Treg-polarizing conditions and promoted Treg differentiation. Model: Mouse naive T-cell differentiation, chromatin measurements and colitis experiments. Limitations: Not a claim that butyrate turns every T cell into a Treg or universally suppresses immunity. Correction record: Publisher correction reviewed: Figure 1d upper-right axis identifies Neuropilin-1-positive Foxp3-positive cells; the originally printed negative-marker label was wrong. The notice does not amend the Foxp3 histone-acetylation result cited here. https://www.nature.com/articles/nature13041 Evidence access: Primary abstract Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. · 2013 · https://pubmed.ncbi.nlm.nih.gov/24226770/ · DOI 10.1038/nature12721
Complete structured claim and evidence
The rise in extrathymically generated Tregs after butyrate depended on the Foxp3 CNS1 enhancer in mice.
Mouse Foxp3 CNS1 enhancer function → Mouse extrathymic regulatory T-cell differentiation after butyrate source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Mouse CNS1 genetic experiments.
limitations
Extrathymic differentiation is distinct from thymic Treg generation.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
An intact gene-regulatory element was needed for this differentiation response.
primary_references
Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. · 2013 · https://pubmed.ncbi.nlm.nih.gov/24226773/ · DOI 10.1038/nature12726
trigger_kind
machinery_impairment Imported condition classification; unverified.
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 342–348
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse CNS1 genetic experiments. · source_derived_draft · unverified_draft
## butyrate-cns1-dependency An intact gene-regulatory element was needed for this differentiation response. The rise in extrathymically generated Tregs after butyrate depended on the Foxp3 CNS1 enhancer in mice. Model: Mouse CNS1 genetic experiments. Limitations: Extrathymic differentiation is distinct from thymic Treg generation. Evidence access: Primary abstract Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. · 2013 · https://pubmed.ncbi.nlm.nih.gov/24226773/ · DOI 10.1038/nature12726
Complete structured claim and evidence
Butyrate activated GPR109A/HCAR2 at millimolar concentrations in the study of receptor signaling in human colonic cells.
Butyrate → Human hydroxycarboxylic acid receptor 2 / HCAR2 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human receptor/cell assays with separate mouse tissue observations.
limitations
Low affinity makes exposure compartment important; sharing a receptor does not make butyrate and niacin nutritionally interchangeable.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
A receptor also used by nicotinic acid senses sufficiently high local butyrate.
primary_references
GPR109A is a G-protein-coupled receptor for the bacterial fermentation product butyrate and functions as a tumor suppressor in colon. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19276343/ · DOI 10.1158/0008-5472.CAN-08-4466
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 350–356
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human receptor/cell assays with separate mouse tissue observations. · source_derived_draft · unverified_draft
## butyrate-hcar2-agonism A receptor also used by nicotinic acid senses sufficiently high local butyrate. Butyrate activated GPR109A/HCAR2 at millimolar concentrations in the study of receptor signaling in human colonic cells. Model: Human receptor/cell assays with separate mouse tissue observations. Limitations: Low affinity makes exposure compartment important; sharing a receptor does not make butyrate and niacin nutritionally interchangeable. Evidence access: Primary abstract GPR109A is a G-protein-coupled receptor for the bacterial fermentation product butyrate and functions as a tumor suppressor in colon. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19276343/ · DOI 10.1158/0008-5472.CAN-08-4466
Complete structured claim and evidence
Restoring GPR109A expression in human colon cancer cells enabled apoptosis in the presence of butyrate or nicotinate; the receptor-mediated response did not require histone deacetylation inhibition.
Human hydroxycarboxylic acid receptor 2 / HCAR2 → Apoptosis in human colon cancer cells with restored HCAR2 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human colon cancer-cell receptor reexpression.
limitations
An engineered culture rescue does not show that oral supplements restore silenced receptors in patients.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
Restoring the receptor enabled a response distinct from the HDAC pathway.
primary_references
GPR109A is a G-protein-coupled receptor for the bacterial fermentation product butyrate and functions as a tumor suppressor in colon. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19276343/ · DOI 10.1158/0008-5472.CAN-08-4466
trigger_kind
machinery_impairment Imported condition classification; unverified.
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 358–364
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human colon cancer-cell receptor reexpression. · source_derived_draft · unverified_draft
## butyrate-hcar2-restoration Restoring the receptor enabled a response distinct from the HDAC pathway. Restoring GPR109A expression in human colon cancer cells enabled apoptosis in the presence of butyrate or nicotinate; the receptor-mediated response did not require histone deacetylation inhibition. Model: Human colon cancer-cell receptor reexpression. Limitations: An engineered culture rescue does not show that oral supplements restore silenced receptors in patients. Evidence access: Primary abstract GPR109A is a G-protein-coupled receptor for the bacterial fermentation product butyrate and functions as a tumor suppressor in colon. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19276343/ · DOI 10.1158/0008-5472.CAN-08-4466
Complete structured claim and evidence
Butyrate promoted Aldh1a1 and Il10 expression in mouse dendritic/macrophage experiments through Gpr109a signaling.
Butyrate → Mouse aldehyde dehydrogenase 1 family member A1 / Aldh1a1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text, Figure 2
experimental_model
Mouse immune-cell stimulation and Hcar2-deficient comparisons.
limitations
ALDH expression does not by itself measure retinoic-acid flux or establish dietary vitamin A deficiency.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
A butyrate signal connected to vitamin A processing and immune regulation.
primary_references
Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24412617/ · DOI 10.1016/j.immuni.2013.12.007
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 366–372
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse immune-cell stimulation and Hcar2-deficient comparisons. · source_derived_draft · unverified_draft
## butyrate-aldh1a1-immune A butyrate signal connected to vitamin A processing and immune regulation. Butyrate promoted Aldh1a1 and Il10 expression in mouse dendritic/macrophage experiments through Gpr109a signaling. Model: Mouse immune-cell stimulation and Hcar2-deficient comparisons. Limitations: ALDH expression does not by itself measure retinoic-acid flux or establish dietary vitamin A deficiency. Evidence access: Primary full text, Figure 2 Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24412617/ · DOI 10.1016/j.immuni.2013.12.007
Complete structured claim and evidence
The retinoic-acid-receptor antagonist LE135 abolished the increased Treg conversion induced by butyrate- or niacin-treated wild-type mouse dendritic cells.
Mouse retinoic-acid-receptor signaling in butyrate/DC experiments; receptor subtype unresolved → Mouse extrathymic regulatory T-cell differentiation after butyrate source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text, Figure S2I and methods
experimental_model
Mouse dendritic/T-cell coculture; LE135 1 micromolar.
limitations
Antagonist exposure is not a vitamin A withdrawal experiment; extra vitamin A was not demonstrated to improve a replete response.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
Blocking vitamin A–related receptor signaling removed this immune-cell response.
primary_references
Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24412617/ · DOI 10.1016/j.immuni.2013.12.007
trigger_kind
machinery_impairment Imported condition classification; unverified.
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 374–380
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse dendritic/T-cell coculture; LE135 1 micromolar. · source_derived_draft · unverified_draft
## butyrate-retinoid-block Blocking vitamin A–related receptor signaling removed this immune-cell response. The retinoic-acid-receptor antagonist LE135 abolished the increased Treg conversion induced by butyrate- or niacin-treated wild-type mouse dendritic cells. Model: Mouse dendritic/T-cell coculture; LE135 1 micromolar. Limitations: Antagonist exposure is not a vitamin A withdrawal experiment; extra vitamin A was not demonstrated to improve a replete response. Evidence access: Primary full text, Figure S2I and methods Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24412617/ · DOI 10.1016/j.immuni.2013.12.007
Complete structured claim and evidence
Butyrate-induced Il18 expression in mouse colonic epithelium required Gpr109a/Hcar2.
Mouse Hcar2 / PUMA-G receptor → Mouse interleukin-18 / Il18 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Mouse Hcar2 knockout and epithelial stimulation.
limitations
IL-18 has context-dependent functions; this does not mean all inflammasome activation is beneficial.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
Receptor loss removed a specific epithelial cytokine response.
primary_references
Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24412617/ · DOI 10.1016/j.immuni.2013.12.007
trigger_kind
machinery_impairment Imported condition classification; unverified.
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 382–388
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse Hcar2 knockout and epithelial stimulation. · source_derived_draft · unverified_draft
## butyrate-hcar2-il18 Receptor loss removed a specific epithelial cytokine response. Butyrate-induced Il18 expression in mouse colonic epithelium required Gpr109a/Hcar2. Model: Mouse Hcar2 knockout and epithelial stimulation. Limitations: IL-18 has context-dependent functions; this does not mean all inflammasome activation is beneficial. Evidence access: Primary abstract Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24412617/ · DOI 10.1016/j.immuni.2013.12.007
Complete structured claim and evidence
Differentiating human blood monocytes with butyrate enhanced subsequent macrophage antibacterial activity without increasing inflammatory cytokine output.
Butyrate → Antimicrobial activity of butyrate-differentiated human macrophages source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text, human macrophage differentiation/results
experimental_model
Human donor monocyte-derived macrophages.
limitations
Differentiation exposure is different from acute dosing of mature cells or treating an infection in a patient.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
Microbe killing and inflammatory signaling changed independently.
primary_references
The Short Chain Fatty Acid Butyrate Imprints an Antimicrobial Program in Macrophages. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30683619/ · DOI 10.1016/j.immuni.2018.12.018
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 390–396
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human donor monocyte-derived macrophages. · source_derived_draft · unverified_draft
## butyrate-macrophage-killing Microbe killing and inflammatory signaling changed independently. Differentiating human blood monocytes with butyrate enhanced subsequent macrophage antibacterial activity without increasing inflammatory cytokine output. Model: Human donor monocyte-derived macrophages. Limitations: Differentiation exposure is different from acute dosing of mature cells or treating an infection in a patient. Evidence access: Primary full text, human macrophage differentiation/results The Short Chain Fatty Acid Butyrate Imprints an Antimicrobial Program in Macrophages. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30683619/ · DOI 10.1016/j.immuni.2018.12.018
Complete structured claim and evidence
HDAC3 inhibition and HDAC3 siRNA supported the HDAC3-dependent differentiation program induced by butyrate in human macrophages.
Butyrate → Human histone deacetylase 3 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text, Figure 5
experimental_model
Human donor macrophages; HDAC inhibitors and gene silencing.
limitations
Does not imply butyrate is selective for HDAC3 in every tissue.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
A chromatin enzyme helped explain the antimicrobial program.
primary_references
The Short Chain Fatty Acid Butyrate Imprints an Antimicrobial Program in Macrophages. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30683619/ · DOI 10.1016/j.immuni.2018.12.018
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 398–404
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human donor macrophages; HDAC inhibitors and gene silencing. · source_derived_draft · unverified_draft
## butyrate-macrophage-hdac3 A chromatin enzyme helped explain the antimicrobial program. HDAC3 inhibition and HDAC3 siRNA supported the HDAC3-dependent differentiation program induced by butyrate in human macrophages. Model: Human donor macrophages; HDAC inhibitors and gene silencing. Limitations: Does not imply butyrate is selective for HDAC3 in every tissue. Evidence access: Primary full text, Figure 5 The Short Chain Fatty Acid Butyrate Imprints an Antimicrobial Program in Macrophages. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30683619/ · DOI 10.1016/j.immuni.2018.12.018
Complete structured claim and evidence
Butyrate-differentiated macrophages showed reduced mTOR activity, increased LC3-associated defense and antimicrobial peptide expression alongside metabolic remodeling.
Butyrate → Metabolic program of butyrate-differentiated human macrophages source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human monocyte/macrophage experiments.
limitations
LC3 association is not by itself proof of increased complete autophagic flux or direct butyrate binding to mTOR.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
The immune cells changed both their fuel program and defensive machinery.
primary_references
The Short Chain Fatty Acid Butyrate Imprints an Antimicrobial Program in Macrophages. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30683619/ · DOI 10.1016/j.immuni.2018.12.018
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 406–412
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human monocyte/macrophage experiments. · source_derived_draft · unverified_draft
## butyrate-macrophage-metabolism The immune cells changed both their fuel program and defensive machinery. Butyrate-differentiated macrophages showed reduced mTOR activity, increased LC3-associated defense and antimicrobial peptide expression alongside metabolic remodeling. Model: Human monocyte/macrophage experiments. Limitations: LC3 association is not by itself proof of increased complete autophagic flux or direct butyrate binding to mTOR. Evidence access: Primary abstract The Short Chain Fatty Acid Butyrate Imprints an Antimicrobial Program in Macrophages. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30683619/ · DOI 10.1016/j.immuni.2018.12.018
Complete structured claim and evidence
Butyrate reduced TNF and IL-6 secretion by more than 50% in ex-vivo inflamed human IBD biopsies.
Butyrate → Cytokine output of butyrate-treated human IBD biopsies source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human IBD biopsy culture.
limitations
Ex-vivo response is not a randomized clinical remission result.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
Inflamed patient tissue released less of two cytokines in culture.
primary_references
Butyrate suppresses mucosal inflammation in inflammatory bowel disease primarily through HDAC3 inhibition in monocytes and macrophages. · 2025 · https://pubmed.ncbi.nlm.nih.gov/41110099/ · DOI 10.1111/febs.70289
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 414–420
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human IBD biopsy culture. · source_derived_draft · unverified_draft
## butyrate-ibd-biopsy-cytokines Inflamed patient tissue released less of two cytokines in culture. Butyrate reduced TNF and IL-6 secretion by more than 50% in ex-vivo inflamed human IBD biopsies. Model: Human IBD biopsy culture. Limitations: Ex-vivo response is not a randomized clinical remission result. Evidence access: Primary abstract Butyrate suppresses mucosal inflammation in inflammatory bowel disease primarily through HDAC3 inhibition in monocytes and macrophages. · 2025 · https://pubmed.ncbi.nlm.nih.gov/41110099/ · DOI 10.1111/febs.70289
Complete structured claim and evidence
Butyrate restored MCT1 and IL-18 expression in challenged human epithelial organoids, but did not suppress their pro-inflammatory gene expression as it did in mononuclear-cell experiments.
Butyrate → Epithelial response to butyrate in human IBD tissue and organoid experiments source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human organoids, mucosa and mononuclear-cell comparisons.
limitations
MCT1 recovery and immune-cell cytokine suppression are separate endpoints.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
Cell identity changed which effects were seen.
primary_references
Butyrate suppresses mucosal inflammation in inflammatory bowel disease primarily through HDAC3 inhibition in monocytes and macrophages. · 2025 · https://pubmed.ncbi.nlm.nih.gov/41110099/ · DOI 10.1111/febs.70289
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 422–428
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human organoids, mucosa and mononuclear-cell comparisons. · source_derived_draft · unverified_draft
## butyrate-ibd-epithelial-limit Cell identity changed which effects were seen. Butyrate restored MCT1 and IL-18 expression in challenged human epithelial organoids, but did not suppress their pro-inflammatory gene expression as it did in mononuclear-cell experiments. Model: Human organoids, mucosa and mononuclear-cell comparisons. Limitations: MCT1 recovery and immune-cell cytokine suppression are separate endpoints. Evidence access: Primary abstract Butyrate suppresses mucosal inflammation in inflammatory bowel disease primarily through HDAC3 inhibition in monocytes and macrophages. · 2025 · https://pubmed.ncbi.nlm.nih.gov/41110099/ · DOI 10.1111/febs.70289
Complete structured claim and evidence
GPR109A/G-protein inhibition did not remove the tested human monocyte/macrophage anti-inflammatory response to butyrate; HDAC3-related mechanisms were implicated.
Butyrate → Cytokine output of butyrate-treated human IBD biopsies source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human monocytes and THP-1 macrophage experiments.
limitations
This does not negate the distinct mouse epithelial IL-18 dependency.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
A receptor important in some models was not required for this tested response.
primary_references
Butyrate suppresses mucosal inflammation in inflammatory bowel disease primarily through HDAC3 inhibition in monocytes and macrophages. · 2025 · https://pubmed.ncbi.nlm.nih.gov/41110099/ · DOI 10.1111/febs.70289
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 430–436
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human monocytes and THP-1 macrophage experiments. · source_derived_draft · unverified_draft
## butyrate-ibd-hcar2-not-required A receptor important in some models was not required for this tested response. GPR109A/G-protein inhibition did not remove the tested human monocyte/macrophage anti-inflammatory response to butyrate; HDAC3-related mechanisms were implicated. Model: Human monocytes and THP-1 macrophage experiments. Limitations: This does not negate the distinct mouse epithelial IL-18 dependency. Evidence access: Primary abstract Butyrate suppresses mucosal inflammation in inflammatory bowel disease primarily through HDAC3 inhibition in monocytes and macrophages. · 2025 · https://pubmed.ncbi.nlm.nih.gov/41110099/ · DOI 10.1111/febs.70289
Complete structured claim and evidence
Butyrate exposure during human monocyte differentiation increased S100A8/S100A9 expression and calprotectin protein in the resulting macrophages.
Butyrate → Human S100A8/S100A9 calprotectin complex source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text, Figure 4 and results
experimental_model
Human donor monocyte-derived macrophages.
limitations
Expression alone does not identify which antimicrobial chemical mechanism operated.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
The cells produced more of a two-protein antimicrobial complex.
primary_references
The Short Chain Fatty Acid Butyrate Imprints an Antimicrobial Program in Macrophages. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30683619/ · DOI 10.1016/j.immuni.2018.12.018
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 438–444
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human donor monocyte-derived macrophages. · source_derived_draft · unverified_draft
## butyrate-calprotectin-expression The cells produced more of a two-protein antimicrobial complex. Butyrate exposure during human monocyte differentiation increased S100A8/S100A9 expression and calprotectin protein in the resulting macrophages. Model: Human donor monocyte-derived macrophages. Limitations: Expression alone does not identify which antimicrobial chemical mechanism operated. Evidence access: Primary full text, Figure 4 and results The Short Chain Fatty Acid Butyrate Imprints an Antimicrobial Program in Macrophages. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30683619/ · DOI 10.1016/j.immuni.2018.12.018
Complete structured claim and evidence
Combined S100A8/S100A9 siRNA increased the intracellular bacterial load in butyrate-differentiated human macrophages.
Human S100A8/S100A9 calprotectin complex → Antimicrobial activity of butyrate-differentiated human macrophages source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text, Figure 4G and results
experimental_model
Human macrophages, dual gene silencing and Salmonella gentamicin-protection assay.
limitations
This perturbation supports a calprotectin contribution; it does not isolate zinc or manganese sequestration as the operative mechanism.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
Reducing both components weakened the antimicrobial response.
primary_references
The Short Chain Fatty Acid Butyrate Imprints an Antimicrobial Program in Macrophages. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30683619/ · DOI 10.1016/j.immuni.2018.12.018
trigger_kind
machinery_impairment Imported condition classification; unverified.
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 446–452
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human macrophages, dual gene silencing and Salmonella gentamicin-protection assay. · source_derived_draft · unverified_draft
## butyrate-calprotectin-silencing Reducing both components weakened the antimicrobial response. Combined S100A8/S100A9 siRNA increased the intracellular bacterial load in butyrate-differentiated human macrophages. Model: Human macrophages, dual gene silencing and Salmonella gentamicin-protection assay. Limitations: This perturbation supports a calprotectin contribution; it does not isolate zinc or manganese sequestration as the operative mechanism. Evidence access: Primary full text, Figure 4G and results The Short Chain Fatty Acid Butyrate Imprints an Antimicrobial Program in Macrophages. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30683619/ · DOI 10.1016/j.immuni.2018.12.018
Complete structured claim and evidence
Butyrate expanded gut and bone-marrow Tregs; their interaction with CD8 T cells increased Wnt10b production and bone formation in young mice.
Butyrate → Mouse bone formation after butyrate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Young eugonadic mice; butyrate and separate probiotic interventions.
limitations
No human fracture-prevention result; mineral substrate requirements were not tested.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
An immune-cell relay connected a gut metabolite to bone-building signals.
primary_references
The Microbial Metabolite Butyrate Stimulates Bone Formation via T Regulatory Cell-Mediated Regulation of WNT10B Expression. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30446387/ · DOI 10.1016/j.immuni.2018.10.013
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 454–460
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Young eugonadic mice; butyrate and separate probiotic interventions. · source_derived_draft · unverified_draft
## butyrate-bone-treg-wnt An immune-cell relay connected a gut metabolite to bone-building signals. Butyrate expanded gut and bone-marrow Tregs; their interaction with CD8 T cells increased Wnt10b production and bone formation in young mice. Model: Young eugonadic mice; butyrate and separate probiotic interventions. Limitations: No human fracture-prevention result; mineral substrate requirements were not tested. Evidence access: Primary abstract The Microbial Metabolite Butyrate Stimulates Bone Formation via T Regulatory Cell-Mediated Regulation of WNT10B Expression. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30446387/ · DOI 10.1016/j.immuni.2018.10.013
Complete structured claim and evidence
Tregs promoted NFAT1-SMAD3 complex assembly in mouse CD8 cells, driving Wnt10b expression in the butyrate-associated bone pathway.
Mouse NFAT1 / Nfatc2 → Mouse Wnt family member 10B / Wnt10b source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mouse CD8/Treg mechanistic experiments.
limitations
NFAT1 is Nfatc2, not the osteoclast NFATc1 protein.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
Two transcription factors linked the immune relay to a bone-building ligand.
primary_references
The Microbial Metabolite Butyrate Stimulates Bone Formation via T Regulatory Cell-Mediated Regulation of WNT10B Expression. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30446387/ · DOI 10.1016/j.immuni.2018.10.013
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 462–468
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse CD8/Treg mechanistic experiments. · source_derived_draft · unverified_draft
## butyrate-wnt-transcription-complex Two transcription factors linked the immune relay to a bone-building ligand. Tregs promoted NFAT1-SMAD3 complex assembly in mouse CD8 cells, driving Wnt10b expression in the butyrate-associated bone pathway. Model: Mouse CD8/Treg mechanistic experiments. Limitations: NFAT1 is Nfatc2, not the osteoclast NFATc1 protein. Evidence access: Primary abstract The Microbial Metabolite Butyrate Stimulates Bone Formation via T Regulatory Cell-Mediated Regulation of WNT10B Expression. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30446387/ · DOI 10.1016/j.immuni.2018.10.013
Complete structured claim and evidence
Reconstituting TCR-beta-deficient mice with Wnt10b-deficient CD8 T cells prevented butyrate-induced bone formation and mass acquisition; lowering Treg numbers also prevented the response.
Mouse Wnt family member 10B / Wnt10b → Mouse bone formation after butyrate source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Mouse cellular reconstitution and Treg reduction.
limitations
A genetic dependency is not evidence that a person needs more dietary calcium.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
Butyrate could not replace the missing immune-cell signal.
primary_references
The Microbial Metabolite Butyrate Stimulates Bone Formation via T Regulatory Cell-Mediated Regulation of WNT10B Expression. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30446387/ · DOI 10.1016/j.immuni.2018.10.013
trigger_kind
machinery_impairment Imported condition classification; unverified.
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 470–476
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse cellular reconstitution and Treg reduction. · source_derived_draft · unverified_draft
## butyrate-bone-wnt-loss Butyrate could not replace the missing immune-cell signal. Reconstituting TCR-beta-deficient mice with Wnt10b-deficient CD8 T cells prevented butyrate-induced bone formation and mass acquisition; lowering Treg numbers also prevented the response. Model: Mouse cellular reconstitution and Treg reduction. Limitations: A genetic dependency is not evidence that a person needs more dietary calcium. Evidence access: Primary abstract The Microbial Metabolite Butyrate Stimulates Bone Formation via T Regulatory Cell-Mediated Regulation of WNT10B Expression. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30446387/ · DOI 10.1016/j.immuni.2018.10.013
Complete structured claim and evidence
Butyrate and propionate shifted osteoclast metabolism toward glycolysis, reduced Traf6/Nfatc1 expression and suppressed osteoclast differentiation in the reported experiments.
Butyrate → Mouse osteoclast differentiation after butyrate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mouse osteoclast cultures and bone-loss interventions.
limitations
Distinct from the Treg/Wnt10b bone-formation study; neither proves a universal change in all bone cells.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
A separate pathway reduced bone breakdown rather than increasing bone building.
primary_references
Short-chain fatty acids regulate systemic bone mass and protect from pathological bone loss. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29302038/ · DOI 10.1038/s41467-017-02490-4
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 478–484
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse osteoclast cultures and bone-loss interventions. · source_derived_draft · unverified_draft
## butyrate-osteoclast-metabolism A separate pathway reduced bone breakdown rather than increasing bone building. Butyrate and propionate shifted osteoclast metabolism toward glycolysis, reduced Traf6/Nfatc1 expression and suppressed osteoclast differentiation in the reported experiments. Model: Mouse osteoclast cultures and bone-loss interventions. Limitations: Distinct from the Treg/Wnt10b bone-formation study; neither proves a universal change in all bone cells. Evidence access: Primary abstract Short-chain fatty acids regulate systemic bone mass and protect from pathological bone loss. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29302038/ · DOI 10.1038/s41467-017-02490-4
Complete structured claim and evidence
Antibiotic-depleted or germ-free female mice lost the bone-anabolic response to intermittent PTH; restoring physiological butyrate levels restored the response.
Butyrate → Mouse bone-anabolic response to intermittent PTH source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary abstract and full-text intervention methods
experimental_model
Female mice; microbial depletion, daily subcutaneous human PTH(1-34) at 80 micrograms/kg for four weeks; 5 mM butyrate repletion in drinking water.
limitations
Not proof that human PTH treatment failure is usually butyrate deficiency, or that butyrate replaces PTH, calcium or vitamin D.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
In this mouse model, the hormone response depended on a microbial metabolite.
primary_references
Parathyroid hormone-dependent bone formation requires butyrate production by intestinal microbiota. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31917685/ · DOI 10.1172/JCI133473
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 486–492
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Female mice; microbial depletion, daily subcutaneous human PTH(1-34) at 80 micrograms/kg for four weeks; 5 mM butyrate repletion in drinking water. · source_derived_draft · unverified_draft
## butyrate-pth-microbial-depletion In this mouse model, the hormone response depended on a microbial metabolite. Antibiotic-depleted or germ-free female mice lost the bone-anabolic response to intermittent PTH; restoring physiological butyrate levels restored the response. Model: Female mice; microbial depletion, daily subcutaneous human PTH(1-34) at 80 micrograms/kg for four weeks; 5 mM butyrate repletion in drinking water. Limitations: Not proof that human PTH treatment failure is usually butyrate deficiency, or that butyrate replaces PTH, calcium or vitamin D. Evidence access: Primary abstract and full-text intervention methods Parathyroid hormone-dependent bone formation requires butyrate production by intestinal microbiota. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31917685/ · DOI 10.1172/JCI133473
Complete structured claim and evidence
The permissive butyrate response involved GPR43 signaling in dendritic cells and GPR43-independent effects in T cells in the PTH study.
Mouse free fatty acid receptor 2 / Ffar2 → Mouse bone-anabolic response to intermittent PTH source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mouse cell-specific receptor and PTH experiments.
limitations
Do not assign every T-cell butyrate response to FFAR2.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
The same pathway used different signaling routes in different immune cells.
primary_references
Parathyroid hormone-dependent bone formation requires butyrate production by intestinal microbiota. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31917685/ · DOI 10.1172/JCI133473
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 494–500
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse cell-specific receptor and PTH experiments. · source_derived_draft · unverified_draft
## butyrate-pth-ffar2 The same pathway used different signaling routes in different immune cells. The permissive butyrate response involved GPR43 signaling in dendritic cells and GPR43-independent effects in T cells in the PTH study. Model: Mouse cell-specific receptor and PTH experiments. Limitations: Do not assign every T-cell butyrate response to FFAR2. Evidence access: Primary abstract Parathyroid hormone-dependent bone formation requires butyrate production by intestinal microbiota. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31917685/ · DOI 10.1172/JCI133473
Complete structured claim and evidence
Butyrate activated human GPR43/FFAR2 in the receptor-deorphanization assays.
Butyrate → Human free fatty acid receptor 2 / FFAR2 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human receptor expressed in yeast, mammalian cells and oocyte signaling systems.
limitations
Receptor activation alone does not establish a downstream clinical effect.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
One cell-surface receptor detects short-chain fatty acids.
primary_references
The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12496283/ · DOI 10.1074/jbc.M211609200
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 502–508
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human receptor expressed in yeast, mammalian cells and oocyte signaling systems. · source_derived_draft · unverified_draft
## butyrate-ffar2-agonist One cell-surface receptor detects short-chain fatty acids. Butyrate activated human GPR43/FFAR2 in the receptor-deorphanization assays. Model: Human receptor expressed in yeast, mammalian cells and oocyte signaling systems. Limitations: Receptor activation alone does not establish a downstream clinical effect. Evidence access: Primary abstract The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12496283/ · DOI 10.1074/jbc.M211609200
Complete structured claim and evidence
Butyrate was an agonist at human GPR41/FFAR3, whose chain-length preference differed from GPR43.
Butyrate → Human free fatty acid receptor 3 / FFAR3 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human recombinant receptor signaling assays.
limitations
FFAR3 and FFAR2 are separate proteins, not alternative names for one receptor.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
A second receptor recognized overlapping molecules with different preferences.
primary_references
The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12496283/ · DOI 10.1074/jbc.M211609200
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 510–516
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human recombinant receptor signaling assays. · source_derived_draft · unverified_draft
## butyrate-ffar3-agonist A second receptor recognized overlapping molecules with different preferences. Butyrate was an agonist at human GPR41/FFAR3, whose chain-length preference differed from GPR43. Model: Human recombinant receptor signaling assays. Limitations: FFAR3 and FFAR2 are separate proteins, not alternative names for one receptor. Evidence access: Primary abstract The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12496283/ · DOI 10.1074/jbc.M211609200
Complete structured claim and evidence
Butyrate activated intestinal gluconeogenic gene expression through a cAMP-dependent mechanism in the rodent study.
Butyrate → Rodent intestinal gluconeogenic response to butyrate; species unresolved in accessed abstract source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Rodent intestinal metabolism and signaling experiments.
limitations
The paper assigned propionate, not butyrate, the distinct FFAR3-dependent gut-brain route; butyrate is not being labeled a net glucose carbon source.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
A gut glucose-producing pathway contributed to metabolic signaling.
primary_references
Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24412651/ · DOI 10.1016/j.cell.2013.12.016
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 518–524
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Rodent intestinal metabolism and signaling experiments. · source_derived_draft · unverified_draft
## butyrate-ign-camp A gut glucose-producing pathway contributed to metabolic signaling. Butyrate activated intestinal gluconeogenic gene expression through a cAMP-dependent mechanism in the rodent study. Model: Rodent intestinal metabolism and signaling experiments. Limitations: The paper assigned propionate, not butyrate, the distinct FFAR3-dependent gut-brain route; butyrate is not being labeled a net glucose carbon source. Evidence access: Primary abstract Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24412651/ · DOI 10.1016/j.cell.2013.12.016
Complete structured claim and evidence
Mice deficient in intestinal gluconeogenesis lost the weight/glucose benefits of SCFA or soluble-fiber interventions despite similar microbial-composition changes.
Mouse intestinal gluconeogenesis deficiency in the 2014 study → Mouse metabolic response to butyrate/fiber intervention source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Mouse intestinal-gluconeogenesis-deficiency model.
limitations
The accessed abstract groups SCFA/fiber interventions; it does not isolate every downstream effect to butyrate alone.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
Changing the microbiota was insufficient when a host pathway was missing.
primary_references
Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24412651/ · DOI 10.1016/j.cell.2013.12.016
trigger_kind
machinery_impairment Imported condition classification; unverified.
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 526–532
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse intestinal-gluconeogenesis-deficiency model. · source_derived_draft · unverified_draft
## butyrate-ign-loss Changing the microbiota was insufficient when a host pathway was missing. Mice deficient in intestinal gluconeogenesis lost the weight/glucose benefits of SCFA or soluble-fiber interventions despite similar microbial-composition changes. Model: Mouse intestinal-gluconeogenesis-deficiency model. Limitations: The accessed abstract groups SCFA/fiber interventions; it does not isolate every downstream effect to butyrate alone. Evidence access: Primary abstract Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24412651/ · DOI 10.1016/j.cell.2013.12.016
Complete structured claim and evidence
Butyrate administration induced GLP-1/GIP responses and reduced food intake in the mouse study.
Butyrate → Mouse GLP-1/GIP responses to butyrate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mouse dietary and acute SCFA experiments.
limitations
Not a human appetite or weight-loss trial.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
Gut hormone release accompanied reduced feeding.
primary_references
Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22506074/ · DOI 10.1371/journal.pone.0035240
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 534–540
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse dietary and acute SCFA experiments. · source_derived_draft · unverified_draft
## butyrate-gut-hormones Gut hormone release accompanied reduced feeding. Butyrate administration induced GLP-1/GIP responses and reduced food intake in the mouse study. Model: Mouse dietary and acute SCFA experiments. Limitations: Not a human appetite or weight-loss trial. Evidence access: Primary abstract Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22506074/ · DOI 10.1371/journal.pone.0035240
Complete structured claim and evidence
Ffar3-deficient mice retained the body-weight and food-intake effects of butyrate; FFAR3 had only a minor role in the GLP-1 response and was unnecessary for GIP induction.
Mouse free fatty acid receptor 3 / Ffar3 → Mouse food intake after butyrate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mouse Ffar3 knockout intervention.
limitations
A receptor being activated does not make it necessary for every organism-level response.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
Removing one receptor left much of the response intact.
primary_references
Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22506074/ · DOI 10.1371/journal.pone.0035240
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 542–548
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse Ffar3 knockout intervention. · source_derived_draft · unverified_draft
## butyrate-ffar3-loss-residual Removing one receptor left much of the response intact. Ffar3-deficient mice retained the body-weight and food-intake effects of butyrate; FFAR3 had only a minor role in the GLP-1 response and was unnecessary for GIP induction. Model: Mouse Ffar3 knockout intervention. Limitations: A receptor being activated does not make it necessary for every organism-level response. Evidence access: Primary abstract Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22506074/ · DOI 10.1371/journal.pone.0035240
Complete structured claim and evidence
Feeding sodium butyrate at 5% of a high-fat diet increased thermogenesis and mitochondrial adaptation in mouse muscle and brown fat, with increased PGC-1alpha expression and insulin sensitivity.
Butyrate → Mouse thermogenesis and mitochondrial adaptation after butyrate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
High-fat-fed C57BL/6J mice.
limitations
Five percent of diet is not a human supplement dose; this study did not observe reduced food intake.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
A high dietary exposure changed energy expenditure in mice.
primary_references
Butyrate improves insulin sensitivity and increases energy expenditure in mice. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19366864/ · DOI 10.2337/db08-1637
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 550–556
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · High-fat-fed C57BL/6J mice. · source_derived_draft · unverified_draft
## butyrate-mouse-thermogenesis A high dietary exposure changed energy expenditure in mice. Feeding sodium butyrate at 5% of a high-fat diet increased thermogenesis and mitochondrial adaptation in mouse muscle and brown fat, with increased PGC-1alpha expression and insulin sensitivity. Model: High-fat-fed C57BL/6J mice. Limitations: Five percent of diet is not a human supplement dose; this study did not observe reduced food intake. Evidence access: Primary abstract Butyrate improves insulin sensitivity and increases energy expenditure in mice. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19366864/ · DOI 10.2337/db08-1637
Complete structured claim and evidence
In nine lean men, four weeks of 4 g/day oral sodium butyrate was associated with improved peripheral and hepatic insulin sensitivity.
Butyrate → Human insulin sensitivity after oral sodium butyrate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Uncontrolled before/after pilot with clamp measurements.
limitations
No placebo group; the lean arm cannot establish efficacy in metabolic syndrome.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
A small human pilot detected a metabolic change in lean participants.
primary_references
Differential metabolic effects of oral butyrate treatment in lean versus metabolic syndrome subjects. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29799027/ · DOI 10.1038/s41424-018-0025-4
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 558–564
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Uncontrolled before/after pilot with clamp measurements. · source_derived_draft · unverified_draft
## butyrate-lean-human-insulin A small human pilot detected a metabolic change in lean participants. In nine lean men, four weeks of 4 g/day oral sodium butyrate was associated with improved peripheral and hepatic insulin sensitivity. Model: Uncontrolled before/after pilot with clamp measurements. Limitations: No placebo group; the lean arm cannot establish efficacy in metabolic syndrome. Evidence access: Primary abstract Differential metabolic effects of oral butyrate treatment in lean versus metabolic syndrome subjects. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29799027/ · DOI 10.1038/s41424-018-0025-4
Complete structured claim and evidence
The same 4 g/day, four-week pilot found no insulin-sensitivity improvement in its ten men with metabolic syndrome.
Butyrate → Human insulin sensitivity after oral sodium butyrate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human uncontrolled pilot; separate metabolic-syndrome group.
limitations
Population differences are observed; altered handling is a proposed explanation rather than established mediation.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
The group with metabolic syndrome did not show the lean-group response.
primary_references
Differential metabolic effects of oral butyrate treatment in lean versus metabolic syndrome subjects. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29799027/ · DOI 10.1038/s41424-018-0025-4
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 566–572
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human uncontrolled pilot; separate metabolic-syndrome group. · source_derived_draft · unverified_draft
## butyrate-metabolic-syndrome-null The group with metabolic syndrome did not show the lean-group response. The same 4 g/day, four-week pilot found no insulin-sensitivity improvement in its ten men with metabolic syndrome. Model: Human uncontrolled pilot; separate metabolic-syndrome group. Limitations: Population differences are observed; altered handling is a proposed explanation rather than established mediation. Evidence access: Primary abstract Differential metabolic effects of oral butyrate treatment in lean versus metabolic syndrome subjects. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29799027/ · DOI 10.1038/s41424-018-0025-4
Complete structured claim and evidence
Oral sodium butyrate did not significantly increase brown-adipose glucose uptake in either lean or metabolic-syndrome men in the pilot.
Butyrate → Human brown-adipose glucose uptake after oral butyrate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human FDG-PET/CT before/after measurements.
limitations
FDG uptake is a particular endpoint, not a complete assay of all thermogenesis.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
The expected brown-fat response was not detected.
primary_references
Differential metabolic effects of oral butyrate treatment in lean versus metabolic syndrome subjects. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29799027/ · DOI 10.1038/s41424-018-0025-4
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 574–580
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human FDG-PET/CT before/after measurements. · source_derived_draft · unverified_draft
## butyrate-human-bat-null The expected brown-fat response was not detected. Oral sodium butyrate did not significantly increase brown-adipose glucose uptake in either lean or metabolic-syndrome men in the pilot. Model: Human FDG-PET/CT before/after measurements. Limitations: FDG uptake is a particular endpoint, not a complete assay of all thermogenesis. Evidence access: Primary abstract Differential metabolic effects of oral butyrate treatment in lean versus metabolic syndrome subjects. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29799027/ · DOI 10.1038/s41424-018-0025-4
Complete structured claim and evidence
In 23 hypertensive adults, 3.9 g/day oral sodium butyrate for four weeks increased daytime systolic pressure by 9.63 mmHg and diastolic pressure by 5.08 mmHg versus sodium-matched placebo.
Butyrate → Human blood pressure after butyrate administration source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text, intervention methods and primary results
experimental_model
Double-blind randomized trial after supervised antihypertensive washout; sodium chloride placebo matched the sodium load.
limitations
Small short trial; do not infer the increase was simply unmatched sodium or advise medication changes.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
An oral human trial found higher blood pressure.
primary_references
Effects of Oral Butyrate on Blood Pressure in Patients With Hypertension: A Randomized, Placebo-Controlled Trial. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39034917/ · DOI 10.1161/HYPERTENSIONAHA.123.22437
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 582–588
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Double-blind randomized trial after supervised antihypertensive washout; sodium chloride placebo matched the sodium load. · source_derived_draft · unverified_draft
## butyrate-oral-bp-increase An oral human trial found higher blood pressure. In 23 hypertensive adults, 3.9 g/day oral sodium butyrate for four weeks increased daytime systolic pressure by 9.63 mmHg and diastolic pressure by 5.08 mmHg versus sodium-matched placebo. Model: Double-blind randomized trial after supervised antihypertensive washout; sodium chloride placebo matched the sodium load. Limitations: Small short trial; do not infer the increase was simply unmatched sodium or advise medication changes. Evidence access: Primary full text, intervention methods and primary results Effects of Oral Butyrate on Blood Pressure in Patients With Hypertension: A Randomized, Placebo-Controlled Trial. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39034917/ · DOI 10.1161/HYPERTENSIONAHA.123.22437
Complete structured claim and evidence
Ten Black adults with stage-1 hypertension had lower daytime systolic pressure after an acute 80 mM butyrate enema in a crossover comparison with a 5 mM low-dose enema.
Butyrate → Human blood pressure after butyrate administration source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text, dose/control design and results
experimental_model
Randomized crossover, seven-day separation; 24-hour ambulatory monitoring.
limitations
The comparator contained butyrate, not inert placebo; acute rectal delivery is not four-week oral treatment.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
A small study using a different delivery route found a lower-pressure response.
primary_references
Effect of Acute Gut Butyrate Delivery on Blood Pressure in Black Individuals With Hypertension: A Proof-of-Concept Randomized Controlled Study. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40736085/ · DOI 10.1161/JAHA.124.039759
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 590–596
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Randomized crossover, seven-day separation; 24-hour ambulatory monitoring. · source_derived_draft · unverified_draft
## butyrate-rectal-bp-decrease A small study using a different delivery route found a lower-pressure response. Ten Black adults with stage-1 hypertension had lower daytime systolic pressure after an acute 80 mM butyrate enema in a crossover comparison with a 5 mM low-dose enema. Model: Randomized crossover, seven-day separation; 24-hour ambulatory monitoring. Limitations: The comparator contained butyrate, not inert placebo; acute rectal delivery is not four-week oral treatment. Evidence access: Primary full text, dose/control design and results Effect of Acute Gut Butyrate Delivery on Blood Pressure in Black Individuals With Hypertension: A Proof-of-Concept Randomized Controlled Study. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40736085/ · DOI 10.1161/JAHA.124.039759
Complete structured claim and evidence
Oral butyrate increased plasma butyrate without increasing fecal butyrate in the hypertension trial.
Butyrate → Human circulating butyrate concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Same randomized human oral trial.
limitations
Neither compartment is a universal measure of intracellular sufficiency or total microbial production.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
Blood and stool measurements did not change together.
primary_references
Effects of Oral Butyrate on Blood Pressure in Patients With Hypertension: A Randomized, Placebo-Controlled Trial. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39034917/ · DOI 10.1161/HYPERTENSIONAHA.123.22437
trigger_kind
biomarker_context Imported condition classification; unverified.
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 598–604
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Same randomized human oral trial. · source_derived_draft · unverified_draft
## butyrate-plasma-feces-diverge Blood and stool measurements did not change together. Oral butyrate increased plasma butyrate without increasing fecal butyrate in the hypertension trial. Model: Same randomized human oral trial. Limitations: Neither compartment is a universal measure of intracellular sufficiency or total microbial production. Evidence access: Primary abstract Effects of Oral Butyrate on Blood Pressure in Patients With Hypertension: A Randomized, Placebo-Controlled Trial. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39034917/ · DOI 10.1161/HYPERTENSIONAHA.123.22437
Complete structured claim and evidence
Sodium butyrate reduced proteinuria, podocyte loss and renal injury in the mouse Adriamycin-nephropathy study.
Butyrate → Mouse podocyte injury and proteinuria after butyrate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mouse induced-nephropathy intervention, with a separate butyrate-releasing starch arm.
limitations
Not evidence of efficacy in all human kidney diseases.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
The experimental benefit extended beyond the gut to the kidney.
primary_references
Gut microbial metabolite butyrate protects against proteinuric kidney disease through epigenetic- and GPR109a-mediated mechanisms. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31366236/ · DOI 10.1096/fj.201901080R
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 606–612
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse induced-nephropathy intervention, with a separate butyrate-releasing starch arm. · source_derived_draft · unverified_draft
## butyrate-kidney-protection The experimental benefit extended beyond the gut to the kidney. Sodium butyrate reduced proteinuria, podocyte loss and renal injury in the mouse Adriamycin-nephropathy study. Model: Mouse induced-nephropathy intervention, with a separate butyrate-releasing starch arm. Limitations: Not evidence of efficacy in all human kidney diseases. Evidence access: Primary abstract Gut microbial metabolite butyrate protects against proteinuric kidney disease through epigenetic- and GPR109a-mediated mechanisms. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31366236/ · DOI 10.1096/fj.201901080R
Complete structured claim and evidence
Hcar2-deficient mice lost the reported protective response to butyrate in Adriamycin nephropathy.
Mouse Hcar2 / PUMA-G receptor → Mouse podocyte injury and proteinuria after butyrate source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Mouse receptor knockout during induced nephropathy.
limitations
Does not establish the same dependency for human IBD monocytes or all kidney injury.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
The kidney response required a receptor in this model.
primary_references
Gut microbial metabolite butyrate protects against proteinuric kidney disease through epigenetic- and GPR109a-mediated mechanisms. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31366236/ · DOI 10.1096/fj.201901080R
trigger_kind
machinery_impairment Imported condition classification; unverified.
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 614–620
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse receptor knockout during induced nephropathy. · source_derived_draft · unverified_draft
## butyrate-kidney-hcar2-loss The kidney response required a receptor in this model. Hcar2-deficient mice lost the reported protective response to butyrate in Adriamycin nephropathy. Model: Mouse receptor knockout during induced nephropathy. Limitations: Does not establish the same dependency for human IBD monocytes or all kidney injury. Evidence access: Primary abstract Gut microbial metabolite butyrate protects against proteinuric kidney disease through epigenetic- and GPR109a-mediated mechanisms. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31366236/ · DOI 10.1096/fj.201901080R
Complete structured claim and evidence
Post-training sodium butyrate injection enabled 24-hour object-location memory after otherwise subthreshold training in mice, with increased hippocampal Bdnf transcripts.
Butyrate → Mouse object-location memory after injected sodium butyrate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mouse behavioral and hippocampal transcription experiments.
limitations
Injected pharmacological exposure does not establish that ordinary microbial production or oral supplements improve human memory.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
Injected treatment changed a learning response in mice.
primary_references
Exercise and sodium butyrate transform a subthreshold learning event into long-term memory via a brain-derived neurotrophic factor-dependent mechanism. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23615664/ · DOI 10.1038/npp.2013.104
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 622–628
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse behavioral and hippocampal transcription experiments. · source_derived_draft · unverified_draft
## butyrate-brain-memory Injected treatment changed a learning response in mice. Post-training sodium butyrate injection enabled 24-hour object-location memory after otherwise subthreshold training in mice, with increased hippocampal Bdnf transcripts. Model: Mouse behavioral and hippocampal transcription experiments. Limitations: Injected pharmacological exposure does not establish that ordinary microbial production or oral supplements improve human memory. Evidence access: Primary abstract Exercise and sodium butyrate transform a subthreshold learning event into long-term memory via a brain-derived neurotrophic factor-dependent mechanism. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23615664/ · DOI 10.1038/npp.2013.104
Complete structured claim and evidence
Hippocampal Bdnf siRNA blocked the memory-enabling effect of post-training sodium butyrate in the mouse task.
Mouse brain-derived neurotrophic factor / Bdnf → Mouse object-location memory after injected sodium butyrate source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Mouse hippocampal siRNA and object-location memory assay.
limitations
Task- and intervention-specific; not a universal mechanism for every memory effect of butyrate.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
Reducing a neural growth-factor signal removed the measured benefit.
primary_references
Exercise and sodium butyrate transform a subthreshold learning event into long-term memory via a brain-derived neurotrophic factor-dependent mechanism. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23615664/ · DOI 10.1038/npp.2013.104
trigger_kind
machinery_impairment Imported condition classification; unverified.
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 630–636
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse hippocampal siRNA and object-location memory assay. · source_derived_draft · unverified_draft
## butyrate-bdnf-knockdown Reducing a neural growth-factor signal removed the measured benefit. Hippocampal Bdnf siRNA blocked the memory-enabling effect of post-training sodium butyrate in the mouse task. Model: Mouse hippocampal siRNA and object-location memory assay. Limitations: Task- and intervention-specific; not a universal mechanism for every memory effect of butyrate. Evidence access: Primary abstract Exercise and sodium butyrate transform a subthreshold learning event into long-term memory via a brain-derived neurotrophic factor-dependent mechanism. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23615664/ · DOI 10.1038/npp.2013.104
Complete structured claim and evidence
Carbohydrate-derived microbial metabolites including butyrate fueled hyperproliferation of Msh2-deficient colonic epithelium in the Apc-mutant mouse cancer model.
Butyrate → Proliferation of Apc/Msh2-deficient mouse colonic epithelium source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Apc-mutant/Msh2-deficient mice; dietary and microbial perturbation.
limitations
Genotype-specific model, not proof that butyrate causes cancer in healthy humans or that fiber should be avoided. Correction record: A published erratum is confirmed by PubMed and publisher/Crossref metadata: Cell 159(2):456, 2014. The notice body was not available through the accessed publisher endpoints, so its specific impact has not been assessed. The abstract-based MSH2 claim remains provisional with this unresolved correction flag. https://doi.org/10.1016/j.cell.2014.09.041
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
A genetically altered epithelium could use the metabolite to support abnormal growth.
primary_references
Gut microbial metabolism drives transformation of MSH2-deficient colon epithelial cells. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25036629/ · DOI 10.1016/j.cell.2014.04.051
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 638–644
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Apc-mutant/Msh2-deficient mice; dietary and microbial perturbation. · source_derived_draft · unverified_draft
## butyrate-msh2-context A genetically altered epithelium could use the metabolite to support abnormal growth. Carbohydrate-derived microbial metabolites including butyrate fueled hyperproliferation of Msh2-deficient colonic epithelium in the Apc-mutant mouse cancer model. Model: Apc-mutant/Msh2-deficient mice; dietary and microbial perturbation. Limitations: Genotype-specific model, not proof that butyrate causes cancer in healthy humans or that fiber should be avoided. Correction record: A published erratum is confirmed by PubMed and publisher/Crossref metadata: Cell 159(2):456, 2014. The notice body was not available through the accessed publisher endpoints, so its specific impact has not been assessed. The abstract-based MSH2 claim remains provisional with this unresolved correction flag. https://doi.org/10.1016/j.cell.2014.09.041 Evidence access: Primary abstract Gut microbial metabolism drives transformation of MSH2-deficient colon epithelial cells. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25036629/ · DOI 10.1016/j.cell.2014.04.051
Complete structured claim and evidence
Higher circulating butyrate and propionate were associated with resistance to CTLA-4 blockade in the human cancer cohorts.
Butyrate → Circulating butyrate association with anti-CTLA-4 outcomes in humans source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human observational anti-CTLA-4 cohorts with separate mouse intervention experiments.
limitations
Association is not proof that butyrate supplements caused treatment failure or that findings extend to all immunotherapies.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
A blood-metabolite association accompanied poorer response to one immunotherapy class.
primary_references
Systemic short chain fatty acids limit antitumor effect of CTLA-4 blockade in hosts with cancer. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32358520/ · DOI 10.1038/s41467-020-16079-x
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 646–652
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human observational anti-CTLA-4 cohorts with separate mouse intervention experiments. · source_derived_draft · unverified_draft
## butyrate-ctla4-human A blood-metabolite association accompanied poorer response to one immunotherapy class. Higher circulating butyrate and propionate were associated with resistance to CTLA-4 blockade in the human cancer cohorts. Model: Human observational anti-CTLA-4 cohorts with separate mouse intervention experiments. Limitations: Association is not proof that butyrate supplements caused treatment failure or that findings extend to all immunotherapies. Evidence access: Primary abstract Systemic short chain fatty acids limit antitumor effect of CTLA-4 blockade in hosts with cancer. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32358520/ · DOI 10.1038/s41467-020-16079-x
Complete structured claim and evidence
Butyrate exposure limited anti-CTLA-4 antitumor activity in the mouse experiments.
Butyrate → Mouse anti-CTLA-4 treatment response during butyrate exposure source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Tumor-bearing mice receiving butyrate and checkpoint blockade.
limitations
Mouse exposure and tumor context do not directly define a human drug–supplement effect.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
An intervention supported a treatment interaction in a preclinical model.
primary_references
Systemic short chain fatty acids limit antitumor effect of CTLA-4 blockade in hosts with cancer. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32358520/ · DOI 10.1038/s41467-020-16079-x
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 654–660
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Tumor-bearing mice receiving butyrate and checkpoint blockade. · source_derived_draft · unverified_draft
## butyrate-ctla4-mouse An intervention supported a treatment interaction in a preclinical model. Butyrate exposure limited anti-CTLA-4 antitumor activity in the mouse experiments. Model: Tumor-bearing mice receiving butyrate and checkpoint blockade. Limitations: Mouse exposure and tumor context do not directly define a human drug–supplement effect. Evidence access: Primary abstract Systemic short chain fatty acids limit antitumor effect of CTLA-4 blockade in hosts with cancer. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32358520/ · DOI 10.1038/s41467-020-16079-x
Complete structured claim and evidence
Butyrate restrained anti-CTLA-4-induced dendritic-cell CD80/CD86 and T-cell ICOS upregulation, with fewer tumor-specific and memory T cells in mice.
Butyrate → Mouse dendritic/T-cell costimulation during anti-CTLA-4 treatment source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mouse immunophenotyping during anti-CTLA-4 therapy.
limitations
Reduced signals in this setting are not a universal description of all T-cell responses.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
The proposed interaction involved how immune cells activate one another.
primary_references
Systemic short chain fatty acids limit antitumor effect of CTLA-4 blockade in hosts with cancer. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32358520/ · DOI 10.1038/s41467-020-16079-x
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 662–668
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse immunophenotyping during anti-CTLA-4 therapy. · source_derived_draft · unverified_draft
## butyrate-ctla4-costimulation The proposed interaction involved how immune cells activate one another. Butyrate restrained anti-CTLA-4-induced dendritic-cell CD80/CD86 and T-cell ICOS upregulation, with fewer tumor-specific and memory T cells in mice. Model: Mouse immunophenotyping during anti-CTLA-4 therapy. Limitations: Reduced signals in this setting are not a universal description of all T-cell responses. Evidence access: Primary abstract Systemic short chain fatty acids limit antitumor effect of CTLA-4 blockade in hosts with cancer. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32358520/ · DOI 10.1038/s41467-020-16079-x
Complete structured claim and evidence
In-vitro exposure of CTLs and CAR T cells to butyrate or pentanoate increased mTOR-related activity and inhibited class-I HDAC activity, producing a stronger effector program in the study.
Butyrate → Ex-vivo butyrate-conditioned cytotoxic T-cell product; species specified source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Ex-vivo cytotoxic T-cell programming with preclinical cellular-therapy experiments; species recorded in the primary study.
limitations
The accessed abstract groups two SCFAs and multiple cell products; do not assign every in-vivo benefit exclusively to butyrate or claim oral supplementation improves CAR T therapy.
nutrient_topic
Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
plain_language
Treating cells outside the body was a different intervention from systemic exposure during checkpoint therapy.
primary_references
Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34210970/ · DOI 10.1038/s41467-021-24331-1
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 670–676
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Ex-vivo cytotoxic T-cell programming with preclinical cellular-therapy experiments; species recorded in the primary study. · source_derived_draft · unverified_draft
## butyrate-tcell-conditioning Treating cells outside the body was a different intervention from systemic exposure during checkpoint therapy. In-vitro exposure of CTLs and CAR T cells to butyrate or pentanoate increased mTOR-related activity and inhibited class-I HDAC activity, producing a stronger effector program in the study. Model: Ex-vivo cytotoxic T-cell programming with preclinical cellular-therapy experiments; species recorded in the primary study. Limitations: The accessed abstract groups two SCFAs and multiple cell products; do not assign every in-vivo benefit exclusively to butyrate or claim oral supplementation improves CAR T therapy. Evidence access: Primary abstract Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34210970/ · DOI 10.1038/s41467-021-24331-1
Complete structured claim and evidence
The carrot RG-I model intervention increased butyrate by a reported 4.1 mM.
Carrot pectin extract enriched in RG-I → Butyrate source_derived_draftungraded
Experimental context and source evidence
evidence_span
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experimental_model
M-SHIME simulated colons with four donor microbiotas
exposure
Carrot RG-I extract, 3 g/day for three weeks in the model
limitations
No human host received this regimen in this experiment. Donor-specific cultures and product composition limit extrapolation.
nutrient_topic
Pectin research collection; topical membership is not evidence of a direct dietary effect. · Pectin, structurally heterogeneous plant polysaccharides
organism
Human fecal microbial communities in vitro
plain_language
This particular extract supported microbial production of butyrate in simulated colons.
primary_references
[pectin-p34683463] Consistent Prebiotic Effects of Carrot RG-I on the Gut Microbiota of Four Human Adult Donors in the SHIME® Model despite Baseline Individual Variability. (2021). https://pubmed.ncbi.nlm.nih.gov/34683463/ DOI: 10.3390/microorganisms9102142
tissue_or_cell_type
Simulated colonic compartments
Pectin: metabolism, signaling and nutrient connections (2026-09-17) · lines 932–943
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · M-SHIME simulated colons with four donor microbiotas · source_derived_draft · unverified_draft
### pectin-crgi-butyrate The carrot RG-I model intervention increased butyrate by a reported 4.1 mM. Condition category: normal nutrient_topic: Pectin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This particular extract supported microbial production of butyrate in simulated colons. organism: Human fecal microbial communities in vitro tissue_or_cell_type: Simulated colonic compartments experimental_model: M-SHIME simulated colons with four donor microbiotas limitations: No human host received this regimen in this experiment. Donor-specific cultures and product composition limit extrapolation. exposure: Carrot RG-I extract, 3 g/day for three weeks in the model evidence_span: {"source_cache": "artifacts/pectin-research/34683463.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "38a179d5d001092c0d9595bb3d93ae4fcf8780bb7ae6286e0edfd27971c2aabc", "start_char": 0, "end_char": 1830, "text_sha256": "38a179d5d001092c0d9595bb3d93ae4fcf8780bb7ae6286e0edfd27971c2aabc"} [pectin-p34683463] Consistent Prebiotic Effects of Carrot RG-I on the Gut Microbiota of Four Human Adult Donors in the SHIME® Model despite Baseline Individual Variability. (2021). https://pubmed.ncbi.nlm.nih.gov/34683463/ DOI: 10.3390/microorganisms9102142
Complete structured claim and evidence
Oral berberine increased microbial butyrate production in the animal and bacterial-culture experiments.
Berberine → Gut microbial butyrate production source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/berberine-research/28403947.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cfddc94ff2b2fde20038169c5734cb9d4968c6939ebb94052b9638c8043cc877", "start_char": 0, "end_char": 2151, "text_sha256": "cfddc94ff2b2fde20038169c5734cb9d4968c6939ebb94052b9638c8043cc877"}
experimental_model
Bacterial culture and animal route/antibiotic experiments
exposure
Oral versus intraperitoneal berberine; antibiotics and direct butyrate comparison
limitations
Preclinical evidence. Butyrate production was an indirect microbial route; injected berberine retained separate metabolic effects without raising butyrate. Does not establish probiotic synergy in people.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Gut bacteria and rodents
plain_language
Microbes can turn a drug exposure into a change in metabolite supply.
primary_references
[berberine-p28403947] Berberine-induced bioactive metabolites of the gut microbiota improve energy metabolism. (2017). https://pubmed.ncbi.nlm.nih.gov/28403947/ DOI: 10.1016/j.metabol.2017.02.003
tissue_or_cell_type
Short-chain fatty acid production
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 987–998
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bacterial culture and animal route/antibiotic experiments · source_derived_draft · unverified_draft
### berberine-butyrate-production Oral berberine increased microbial butyrate production in the animal and bacterial-culture experiments. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Microbes can turn a drug exposure into a change in metabolite supply. organism: Gut bacteria and rodents tissue_or_cell_type: Short-chain fatty acid production experimental_model: Bacterial culture and animal route/antibiotic experiments limitations: Preclinical evidence. Butyrate production was an indirect microbial route; injected berberine retained separate metabolic effects without raising butyrate. Does not establish probiotic synergy in people. exposure: Oral versus intraperitoneal berberine; antibiotics and direct butyrate comparison evidence_span: {"source_cache": "artifacts/berberine-research/28403947.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cfddc94ff2b2fde20038169c5734cb9d4968c6939ebb94052b9638c8043cc877", "start_char": 0, "end_char": 2151, "text_sha256": "cfddc94ff2b2fde20038169c5734cb9d4968c6939ebb94052b9638c8043cc877"} [berberine-p28403947] Berberine-induced bioactive metabolites of the gut microbiota improve energy metabolism. (2017). https://pubmed.ncbi.nlm.nih.gov/28403947/ DOI: 10.1016/j.metabol.2017.02.003
Complete structured claim and evidence
Antibiotic pretreatment abolished the berberine-associated rise in butyrate.
Gut bacterial biomass → Gut microbial butyrate production source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/berberine-research/28403947.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cfddc94ff2b2fde20038169c5734cb9d4968c6939ebb94052b9638c8043cc877", "start_char": 0, "end_char": 2151, "text_sha256": "cfddc94ff2b2fde20038169c5734cb9d4968c6939ebb94052b9638c8043cc877"}
experimental_model
Bacterial culture and animal route/antibiotic experiments
exposure
Oral versus intraperitoneal berberine; antibiotics and direct butyrate comparison
limitations
Preclinical evidence. Butyrate production was an indirect microbial route; injected berberine retained separate metabolic effects without raising butyrate. Does not establish probiotic synergy in people.
nutrient_topic
Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine
organism
Gut bacteria and rodents
plain_language
This branch weakened when the organisms producing the metabolite were removed.
primary_references
[berberine-p28403947] Berberine-induced bioactive metabolites of the gut microbiota improve energy metabolism. (2017). https://pubmed.ncbi.nlm.nih.gov/28403947/ DOI: 10.1016/j.metabol.2017.02.003
tissue_or_cell_type
Short-chain fatty acid production
trigger_kind
machinery_impairment Imported condition classification; unverified.
Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 1065–1076
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bacterial culture and animal route/antibiotic experiments · source_derived_draft · unverified_draft
### berberine-butyrate-antibiotics Antibiotic pretreatment abolished the berberine-associated rise in butyrate. Condition category: machinery_impairment nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: This branch weakened when the organisms producing the metabolite were removed. organism: Gut bacteria and rodents tissue_or_cell_type: Short-chain fatty acid production experimental_model: Bacterial culture and animal route/antibiotic experiments limitations: Preclinical evidence. Butyrate production was an indirect microbial route; injected berberine retained separate metabolic effects without raising butyrate. Does not establish probiotic synergy in people. exposure: Oral versus intraperitoneal berberine; antibiotics and direct butyrate comparison evidence_span: {"source_cache": "artifacts/berberine-research/28403947.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cfddc94ff2b2fde20038169c5734cb9d4968c6939ebb94052b9638c8043cc877", "start_char": 0, "end_char": 2151, "text_sha256": "cfddc94ff2b2fde20038169c5734cb9d4968c6939ebb94052b9638c8043cc877"} [berberine-p28403947] Berberine-induced bioactive metabolites of the gut microbiota improve energy metabolism. (2017). https://pubmed.ncbi.nlm.nih.gov/28403947/ DOI: 10.1016/j.metabol.2017.02.003
Complete structured claim and evidence
Nicotinic-acid activation of GPR109A/HCAR2 in the human cell-line assay lowered cAMP through a pertussis-toxin-sensitive pathway.
Human hydroxycarboxylic acid receptor 2 / HCAR2 → Intracellular cyclic AMP content source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Nicotinic acid (agonist); Cyclic adenosine monophosphate (measured_signal)
evidence_span
{"source_cache": "artifacts/niacin-clinical-sources/walters2009.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "2eb822534ed0c8ea9f71ec67288c302e4e375ed9e86cfe70b28f21ae65ffbd4b", "start_char": 0, "end_char": 1537, "text_sha256": "2eb822534ed0c8ea9f71ec67288c302e4e375ed9e86cfe70b28f21ae65ffbd4b"}
experimental_model
Human cell-line nicotinic-acid receptor signaling assay
exposure
Nicotinic-acid stimulation and beta-arrestin perturbation
limitations
Pharmacological receptor signaling, not an essential effect of every B3 precursor. Cell signaling and mouse physiology are distinct arms. Reduced fatty acids or flushing does not establish cardiovascular benefit.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
Nicotinic acid can act as a receptor signal as well as a vitamin precursor, switching down a cellular signaling molecule.
primary_references
[nia-clin-walters2009] beta-Arrestin1 mediates nicotinic acid-induced flushing, but not its antilipolytic effect, in mice. (2009). https://pubmed.ncbi.nlm.nih.gov/19349687/ DOI: 10.1172/jci36806
tissue_or_cell_type
Cultured human cells
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1291–1303
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human cell-line nicotinic-acid receptor signaling assay · source_derived_draft · unverified_draft
### nia-clin-hcar2-camp Nicotinic-acid activation of GPR109A/HCAR2 in the human cell-line assay lowered cAMP through a pertussis-toxin-sensitive pathway. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Nicotinic acid can act as a receptor signal as well as a vitamin precursor, switching down a cellular signaling molecule. organism: Homo sapiens tissue_or_cell_type: Cultured human cells experimental_model: Human cell-line nicotinic-acid receptor signaling assay limitations: Pharmacological receptor signaling, not an essential effect of every B3 precursor. Cell signaling and mouse physiology are distinct arms. Reduced fatty acids or flushing does not establish cardiovascular benefit. exposure: Nicotinic-acid stimulation and beta-arrestin perturbation cross_nutrient: Nicotinic acid (agonist); Cyclic adenosine monophosphate (measured_signal) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/walters2009.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "2eb822534ed0c8ea9f71ec67288c302e4e375ed9e86cfe70b28f21ae65ffbd4b", "start_char": 0, "end_char": 1537, "text_sha256": "2eb822534ed0c8ea9f71ec67288c302e4e375ed9e86cfe70b28f21ae65ffbd4b"} [nia-clin-walters2009] beta-Arrestin1 mediates nicotinic acid-induced flushing, but not its antilipolytic effect, in mice. (2009). https://pubmed.ncbi.nlm.nih.gov/19349687/ DOI: 10.1172/jci36806
Complete structured claim and evidence
D-beta-hydroxybutyrate activated human HM74a/HCAR2 and its mouse orthologue.
D-(R)-beta-hydroxybutyrate → Human hydroxycarboxylic acid receptor 2 / HCAR2 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human and mouse receptor pharmacology.
limitations
Shared receptor does not imply identical exposures or clinical effects.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
A fasting-associated ketone uses a receptor also used by nicotinic acid.
primary_references
(D)-beta-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15929991/ · DOI 10.1074/jbc.C500213200
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 352–358
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human and mouse receptor pharmacology. · source_derived_draft · unverified_draft
## fast-bhb-hcar2 A fasting-associated ketone uses a receptor also used by nicotinic acid. D-beta-hydroxybutyrate activated human HM74a/HCAR2 and its mouse orthologue. Model: Human and mouse receptor pharmacology. Limitations: Shared receptor does not imply identical exposures or clinical effects. Evidence access: Primary abstract (D)-beta-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15929991/ · DOI 10.1074/jbc.C500213200
Complete structured claim and evidence
Purified human PPCS, PPCDC and bifunctional CoA synthase reconstituted CoA synthesis from phosphopantothenate in vitro.
4-Phosphopantothenate → Coenzyme A source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Provides the B5-derived CoA partner required by PDH, OGDH, BCKDH and OADH; simultaneous B1/B5 depletion was not tested.
evidence
[{"paper_key": "daugherty-2002-coa", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Reconstituted human enzyme pathway.
limitations
Cross-pathway connection is biochemical integration, not a tested clinical supplementation interaction.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
Vitamin B5 supplies a separate carrier used after B1-dependent decarboxylation. The experiment starts with phosphorylated B5, so it does not test absorption or the first phosphorylation step.
primary_references
[daugherty-2002-coa] Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics (2002). https://pubmed.ncbi.nlm.nih.gov/11923312/ DOI: 10.1074/jbc.m201708200
tissue_or_cell_type
Purified recombinant enzymes
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 731–743
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Reconstituted human enzyme pathway. · source_derived_draft · unverified_draft
### b1-coa-b5-downstream-biosynthesis Purified human PPCS, PPCDC and bifunctional CoA synthase reconstituted CoA synthesis from phosphopantothenate in vitro. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin B5 supplies a separate carrier used after B1-dependent decarboxylation. The experiment starts with phosphorylated B5, so it does not test absorption or the first phosphorylation step. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzymes experimental_model: Reconstituted human enzyme pathway. limitations: Cross-pathway connection is biochemical integration, not a tested clinical supplementation interaction. evidence: [{"paper_key": "daugherty-2002-coa", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: Provides the B5-derived CoA partner required by PDH, OGDH, BCKDH and OADH; simultaneous B1/B5 depletion was not tested. nutrient: Thiamine (vitamin B1) [daugherty-2002-coa] Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics (2002). https://pubmed.ncbi.nlm.nih.gov/11923312/ DOI: 10.1074/jbc.m201708200
Complete structured claim and evidence
Reconstituted human SLC25A42 transported CoA by counter-exchange and targeted mitochondria, supporting a route for mitochondrial CoA import.
Human mitochondrial coenzyme A transporter SLC25A42 → Coenzyme A source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Human SLC25A42 expressed in E. coli, purified and reconstituted into phospholipid vesicles, plus mitochondrial targeting experiments
exposure
Purified transporter proteoliposomes; substrate concentrations not extracted.
limitations
The experiment established exchange, not uniport. The proposed physiological import direction depends on metabolite gradients; the study does not establish that SLC25A42 is the sole importer.
nutrient_topic
Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)
organism
Homo sapiens
plain_language
Cells need transport machinery to supply the mitochondrial CoA compartment.
primary_references
[b5-bio-slc25a42] A novel member of solute carrier family 25 (SLC25A42) is a transporter of coenzyme A and adenosine 3',5'-diphosphate in human mitochondria. (2009). https://pubmed.ncbi.nlm.nih.gov/19429682/ DOI: 10.1074/jbc.m109.014118
tissue_or_cell_type
Reconstituted phospholipid vesicles and mitochondrial-targeting experiments
transport_effect
raises Counter-exchange transport that the record describes as a route for mitochondrial CoA import.
transport_pool
the mitochondrial matrix Counter-exchange transport that the record describes as a route for mitochondrial CoA import.
Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 704–715
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human SLC25A42 expressed in E. coli, purified and reconstituted into phospholipid vesicles, plus mitochondrial targeting experiments · source_derived_draft · unverified_draft
### b5-bio-slc25a42-exchange Reconstituted human SLC25A42 transported CoA by counter-exchange and targeted mitochondria, supporting a route for mitochondrial CoA import. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cells need transport machinery to supply the mitochondrial CoA compartment. organism: Homo sapiens tissue_or_cell_type: Reconstituted phospholipid vesicles and mitochondrial-targeting experiments experimental_model: Human SLC25A42 expressed in E. coli, purified and reconstituted into phospholipid vesicles, plus mitochondrial targeting experiments limitations: The experiment established exchange, not uniport. The proposed physiological import direction depends on metabolite gradients; the study does not establish that SLC25A42 is the sole importer. exposure: Purified transporter proteoliposomes; substrate concentrations not extracted. cross_nutrient: false [b5-bio-slc25a42] A novel member of solute carrier family 25 (SLC25A42) is a transporter of coenzyme A and adenosine 3',5'-diphosphate in human mitochondria. (2009). https://pubmed.ncbi.nlm.nih.gov/19429682/ DOI: 10.1074/jbc.m109.014118
Complete structured claim and evidence
Short-chain enoyl-CoA hydratase ECHS1 hydrates trans-crotonyl-CoA to (S)-3-hydroxybutyryl-CoA.
Crotonyl-CoA → (S)-3-Hydroxybutyryl-CoA source_derived_draftungraded
Experimental context and source evidence
experimental_model
Crotonyl-CoA hydratase assays in control human fibroblasts
limitations
This shared short-chain reaction can process lysine-derived crotonyl-CoA, but the assay does not trace its carbon from lysine. Disease results are not used to label the control reaction as machinery impairment.
organism
Homo sapiens
plain_language
Water is added across the four-carbon intermediate's double bond.
primary_references
[ferdinandusse2015] Clinical and biochemical characterization of four patients with mutations in ECHS1 (2015). https://link.springer.com/article/10.1186/s13023-015-0290-1 DOI: 10.1186/s13023-015-0290-1
tissue_or_cell_type
Fibroblasts; mitochondrial enzyme
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 357–365
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crotonyl-CoA hydratase assays in control human fibroblasts · source_derived_draft · unverified_draft
### echs1-crotonyl-coa-hydration Short-chain enoyl-CoA hydratase ECHS1 hydrates trans-crotonyl-CoA to (S)-3-hydroxybutyryl-CoA. Plain language: Water is added across the four-carbon intermediate's double bond. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Fibroblasts; mitochondrial enzyme experimental_model: Crotonyl-CoA hydratase assays in control human fibroblasts limitations: This shared short-chain reaction can process lysine-derived crotonyl-CoA, but the assay does not trace its carbon from lysine. Disease results are not used to label the control reaction as machinery impairment. [ferdinandusse2015] Clinical and biochemical characterization of four patients with mutations in ECHS1 (2015). https://link.springer.com/article/10.1186/s13023-015-0290-1 DOI: 10.1186/s13023-015-0290-1
Complete structured claim and evidence
The human HADH homodimer reversibly oxidizes (S)-3-hydroxybutyryl-CoA to acetoacetyl-CoA while reducing NAD+ to NADH.
(S)-3-Hydroxybutyryl-CoA → Acetoacetyl-CoA source_derived_draftungraded
Experimental context and source evidence
experimental_model
Purified recombinant human HADH; substrate/product-cofactor crystal complexes
limitations
HADH is distinct from HADHA and HSD17B10. This shared reversible reaction supports the downstream route but does not quantify lysine-specific flux in people.
organism
Homo sapiens
plain_language
The four-carbon hydroxy intermediate is oxidized to a keto intermediate.
primary_references
[barycki2000] Sequestration of the active site by interdomain shifting. Crystallographic and spectroscopic evidence for distinct conformations of L-3-hydroxyacyl-CoA dehydrogenase (2000). https://pubmed.ncbi.nlm.nih.gov/10840044/ DOI: 10.1074/jbc.M004669200
tissue_or_cell_type
Mitochondrial short-chain hydroxyacyl-CoA metabolism; recombinant protein study
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 367–375
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human HADH; substrate/product-cofactor crystal complexes · source_derived_draft · unverified_draft
### hadh-hydroxybutyryl-coa-oxidation The human HADH homodimer reversibly oxidizes (S)-3-hydroxybutyryl-CoA to acetoacetyl-CoA while reducing NAD+ to NADH. Plain language: The four-carbon hydroxy intermediate is oxidized to a keto intermediate. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Mitochondrial short-chain hydroxyacyl-CoA metabolism; recombinant protein study experimental_model: Purified recombinant human HADH; substrate/product-cofactor crystal complexes limitations: HADH is distinct from HADHA and HSD17B10. This shared reversible reaction supports the downstream route but does not quantify lysine-specific flux in people. [barycki2000] Sequestration of the active site by interdomain shifting. Crystallographic and spectroscopic evidence for distinct conformations of L-3-hydroxyacyl-CoA dehydrogenase (2000). https://pubmed.ncbi.nlm.nih.gov/10840044/ DOI: 10.1074/jbc.M004669200
Complete structured claim and evidence
Ascorbate increased the initial rate and extent of PHD2-catalyzed hydroxylation at both tested human HIF-1 alpha prolyl sites in purified-enzyme peptide experiments.
L-Ascorbate → HIF-1 alpha prolyl hydroxylation source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Primary abstract rate/extent and substrate comparisons
experimental_model
Purified enzyme with human HIF-1 alpha-derived peptide substrate
exposure
Ascorbate versus omission/alternative reducing agents; exact concentrations and enzyme constructs not recovered from primary abstract.
limitations
Peptide hydroxylation does not directly establish HIF degradation or transcription changes in intact cells; ankyrin probe is not physiological HIF.
nutrient_topic
Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C
organism
Human HIF-1 alpha substrate; purified recombinant hydroxylase
plain_language
Vitamin C increased the activity of an isolated oxygen-sensing proline hydroxylase.
primary_references
[c-reg-flashman] Investigating the dependence of the hypoxia-inducible factor hydroxylases (factor inhibiting HIF and prolyl hydroxylase domain 2) on ascorbate and other reducing agents. (2010). https://pubmed.ncbi.nlm.nih.gov/20055761/ DOI: 10.1042/bj20091609
tissue_or_cell_type
Cell-free
Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1117–1129
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified enzyme with human HIF-1 alpha-derived peptide substrate · source_derived_draft · unverified_draft
### c-reg-phd2-ascorbate Ascorbate increased the initial rate and extent of PHD2-catalyzed hydroxylation at both tested human HIF-1 alpha prolyl sites in purified-enzyme peptide experiments. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin C increased the activity of an isolated oxygen-sensing proline hydroxylase. organism: Human HIF-1 alpha substrate; purified recombinant hydroxylase tissue_or_cell_type: Cell-free experimental_model: Purified enzyme with human HIF-1 alpha-derived peptide substrate limitations: Peptide hydroxylation does not directly establish HIF degradation or transcription changes in intact cells; ankyrin probe is not physiological HIF. exposure: Ascorbate versus omission/alternative reducing agents; exact concentrations and enzyme constructs not recovered from primary abstract. cross_nutrient: true evidence_location: Primary abstract rate/extent and substrate comparisons [c-reg-flashman] Investigating the dependence of the hypoxia-inducible factor hydroxylases (factor inhibiting HIF and prolyl hydroxylase domain 2) on ascorbate and other reducing agents. (2010). https://pubmed.ncbi.nlm.nih.gov/20055761/ DOI: 10.1042/bj20091609
Complete structured claim and evidence

Availability and dependencies

Each situation shows the normal role first, then what the sources report under a specific condition. A shortfall in the diet, a fault in the machinery, and a low blood reading are kept separate because they are not the same thing.

Antimicrobial machinery must remain available

Condition: machinery_impairment · Combined S100A8/S100A9 siRNA during the human macrophage experiment.

Normal role: S100A8 and S100A9 form a complex contributing to macrophage antimicrobial function.

Recorded consequence: Intracellular bacterial burden rises in butyrate-differentiated macrophages.

Scope: Human donor macrophages

Microbial depletion can deprive colonocytes of fuel

Condition: nutrient_deficiency · Germ-free mouse status with low microbial metabolite supply.

Normal role: Mature colonocytes oxidize microbial butyrate.

Recorded consequence: Respiration/ATP fall and autophagy increases; butyrate addition rescues these measurements.

Scope: Mouse colonocytes

An ion gradient supports uptake

Condition: machinery_impairment · Removing external sodium in the expression assay.

Normal role: Human SLC5A8 uses external sodium during monocarboxylate transport.

Recorded consequence: Transport-associated current is impaired.

Scope: Human transporter in frog oocytes

Impaired oxidation exposes crypt cells to butyrate

Condition: machinery_impairment · Mouse Acads deletion.

Normal role: Colonocytes consume butyrate before it reaches crypt progenitors.

Recorded consequence: Oxidation falls and the proliferative zone shrinks, further suppressed by butyrate.

Scope: Mouse colonic crypt

Epithelial signaling failure changes bacterial fuel availability

Condition: machinery_impairment · Loss of epithelial Pparg signaling.

Normal role: PPAR-gamma restrains Nos2/nitrate and supports oxidative metabolism.

Recorded consequence: Nos2 and nitrate rise, contributing to a microbial respiratory advantage.

Scope: Mouse colon

AMPK loss removes a barrier response

Condition: machinery_impairment · AMPK siRNA in ethanol-challenged Caco-2 cells.

Normal role: AMPK contributes to the response to butyrate during epithelial challenge.

Recorded consequence: The tested SCFA barrier protection disappears.

Scope: Human cell monolayers

Loss of Foxo3 removes growth suppression

Condition: machinery_impairment · Foxo3 deletion.

Normal role: Foxo3 mediates butyrate-related stem-cell growth suppression.

Recorded consequence: Mouse progenitors resist the proliferation-suppressing effect.

Scope: Mouse crypt stem cells

Immune differentiation requires intact regulatory machinery

Condition: machinery_impairment · Mouse CNS1 loss or RAR antagonism in separate experiments.

Normal role: Foxp3 CNS1 and retinoid signaling support specific Treg responses.

Recorded consequence: Butyrate-associated extrathymic differentiation or dendritic-cell-driven conversion is lost.

Scope: Mouse T-cell differentiation

Receptor status determines specific responses

Condition: machinery_impairment · Mouse Hcar2 loss, or receptor silencing/reexpression in human cancer cells.

Normal role: HCAR2 can mediate epithelial or renal responses.

Recorded consequence: Mouse epithelial IL-18 and renal protection are lost; engineered human receptor restoration enables apoptosis.

Scope: Separate mouse and human cell experiments

Butyrate cannot replace missing Wnt10b signaling

Condition: machinery_impairment · Wnt10b-deficient CD8-cell reconstitution or Treg reduction.

Normal role: Treg/CD8-cell interactions increase Wnt10b in the bone pathway.

Recorded consequence: The butyrate-associated bone-formation response is prevented.

Scope: Mouse bone immunology

Microbial depletion removes a PTH bone response

Condition: nutrient_deficiency · Antibiotic depletion or germ-free status.

Normal role: Butyrate is permissive for intermittent-PTH bone anabolism in mice.

Recorded consequence: PTH-induced bone formation is lost and restored by butyrate repletion.

Scope: Female mouse bone metabolism

A host metabolic pathway is needed downstream of microbes

Condition: machinery_impairment · Mouse intestinal gluconeogenesis deficiency.

Normal role: Intestinal gluconeogenesis relays SCFA/fiber-related metabolic signals.

Recorded consequence: Microbiota changes persist but measured metabolic benefits disappear.

Scope: Mouse metabolic models

A neural response depends on BDNF

Condition: machinery_impairment · Hippocampal Bdnf siRNA.

Normal role: Hippocampal BDNF participates in the tested memory response.

Recorded consequence: Injected sodium butyrate no longer enables subthreshold object-location memory.

Scope: Mouse behavioral experiment

Stool and blood are not interchangeable sufficiency measurements

Condition: biomarker_context · Interpreting fecal or plasma measurements after administration.

Normal role: Uptake and first-pass metabolism separate local from systemic exposure.

Recorded consequence: Colon-delivery systemic availability is low; oral dosing can raise plasma without raising stool butyrate.

Scope: Human pharmacokinetic and trial measurements

The sources

Every document behind this chapter is preserved word for word. Open one to read it in full with its recorded conflicts marked in place.

Berberine: metabolism, nutrient connections and drug interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19)AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · unverified_draftRead preserved source
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18)AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · unverified_draftRead preserved source
L-Lysine: mechanism-first literature curation (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Pectin: metabolism, signaling and nutrient connections (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source

Recorded disagreements

Where two sources say different things, both are kept and the difference is explained. You can discuss a disagreement or propose a mechanism that might account for it.

Why do oral and rectal butyrate studies report different blood-pressure directions?A 2024 randomized sodium-matched oral trial reported increased blood pressure, while a 2025 small acute rectal crossover study reported lower daytime systolic pressure. This is unresolved clinical evidence across different interventions, not a correction to draft wording.Read the recorded disagreement

Open questions in this collection

Questions the curators could not answer from the sources in front of them, kept here with the reason each one is still open. These are gaps in this collection, not findings or proof that no one has studied them.

Chapters are assembled from supplied drafts and curated literature summaries. Statements remain unverified against the primary studies, and the ledger is not medical advice.

Evidence, AI assistance and curation standards

Butyrate

The mechanisms

Butyryl-CoA:acetate CoA-transferase activity was detected in all 38 human-fecal butyrate-producing isolates examined, supporting this terminal route to butyrate.

Only four of 38 examined butyrate-producing isolates had detectable butyrate-kinase activity; the alternative terminal pathway includes phosphotransbutyrylase and butyrate kinase.

Isotope tracing showed external acetate supplied 85–90% of butyrate carbon in the tested F. prausnitzii and Roseburia cultures supplied with 60 mM acetate and 10 mM glucose.

E. hallii-related and A. caccae isolates consumed lactate and formed butyrate; coculture with starch-utilizing B. adolescentis removed detectable L-lactate and generated butyrate.

Adding glucose prevented lactate utilization by the tested lactate-to-butyrate isolates until glucose was exhausted.

In the 174-person two-week fiber study, resistant potato starch produced the greatest fecal SCFA/butyrate rise; resistant maize starch and inulin did not significantly increase fecal butyrate.

Combining the 50 and 100 mg/day riboflavin arms in RIBOGUT showed increased fecal butyrate after two weeks; separate-dose analyses showed only minor SCFA differences.

Colon-delivered isotope tracing in 12 healthy people estimated 24% conversion of acetate into butyrate, the largest measured SCFA interconversion.

Expressing human intestinal SLC5A8 in Xenopus oocytes increased butyrate uptake and generated sodium-dependent inward currents.

Human SMCT/SLC5A8 transport-associated currents depended on external sodium; chloride influenced part of the current but was not cotransported.

Probenecid or ibuprofen at 1 mM strongly inhibited human SLC5A8 activity in the oocyte assay.

At 2 mM sodium butyrate, human AA/C1 colonic cells increased MCT1 mRNA and protein through transcription and greater mRNA stability.

After preincubation with 2 mM sodium butyrate, AA/C1 cells increased the maximal butyrate uptake rate about fivefold without a significant change in apparent Km.

In 12 healthy subjects receiving isotope-labeled SCFAs in colon-release capsules, systemic availability was approximately 2% for butyrate, compared with 9% propionate and 36% acetate.

Butyrate increased apical NHE3 protein and sodium/hydrogen exchange activity in human C2/bbe monolayers, while NHE2 did not increase.

Tributyrin administration replenished colonic butyrate and HIF-related responses in antibiotic-treated mice in the PHD study.

Germ-free mouse colonocytes had reduced NADH/NAD+, oxidative phosphorylation and ATP; adding butyrate rescued mitochondrial respiration.

Butyrate addition prevented energy-stress-associated autophagy in germ-free mouse colonocytes, with fuel use rather than HDAC inhibition explaining the rescue.

In the colonic-cell experiments, butyrate metabolism supplied acetyl-CoA for energy metabolism and histone acetyltransferase activity.

In glycolysis-dominant cancerous colonocytes, reduced butyrate utilization allowed accumulation and HDAC inhibition; altering the metabolic state changed the response.

Butyrate stimulated proliferation in the tested oxidative settings but inhibited proliferation in cells undergoing the Warburg effect.

Acads-deficient colonocytes oxidized less butyrate; knockout mice had a smaller crypt proliferative zone that exogenous butyrate further suppressed.

Microbiota-supported PPAR-gamma signaling drove mouse colonocytes toward beta-oxidation, limiting oxygen available to bacteria in the colonic lumen.

Loss of epithelial PPAR-gamma signaling increased Nos2 expression and colonic nitrate availability in the mouse study.

The mouse experiments linked increased luminal respiratory electron acceptors to expansion of Escherichia and Salmonella when the PPAR-gamma homeostatic pathway was disrupted.

Butyrate increased epithelial oxygen consumption and stabilized HIF in intestinal epithelial-cell experiments.

Butyrate bound and inhibited a recombinant human PHD2 catalytic fragment; kinetic analysis gave a noncompetitive Ki of 5.3 ± 0.5 mM relative to 2-oxoglutarate.

Butyrate still stabilized HIF in human epithelial-cell experiments when its beta-oxidation and associated oxygen consumption were inhibited.

Butyrate increased AMPK activity and accelerated tight-junction assembly in human Caco-2 monolayers; compound C abolished the improvement in electrical resistance.

Sodium butyrate promoted store-operated calcium entry and activated the CaMKK-beta/AMPK pathway during Caco-2 tight-junction reassembly, without the change being explained by ATP concentration.

Sodium butyrate increased PKC-beta2 Ser660 phosphorylation; PKC-beta inhibition blocked the promoted junction reassembly.

Sodium butyrate reduced MLC2 Ser19 phosphorylation during Caco-2 tight-junction reassembly.

AMPK siRNA or compound C removed the barrier protection from SCFA pretreatment, including 2 mM butyrate, against ethanol in Caco-2 cells.

Butyrate inhibited histone decrotonylation in the study linking class-I HDAC activity to crotonylation; separate mouse microbiota depletion altered colonic crotonyl marks.

Direct butyrate exposure suppressed mouse colonic stem/progenitor-cell proliferation; mature colonocytes normally consumed butyrate and limited its access to the crypt base.

When mucosal injury exposed proliferating crypt cells to butyrate, epithelial proliferation and wound repair were delayed in the mouse experiments.

Foxo3 deletion, unlike Foxo1 deletion, made mouse stem/progenitor cells resistant to butyrate-mediated proliferation suppression.

Butyrate increased histone H3 acetylation at Foxp3 regulatory regions under Treg-polarizing conditions and promoted Treg differentiation.

The rise in extrathymically generated Tregs after butyrate depended on the Foxp3 CNS1 enhancer in mice.

Butyrate activated GPR109A/HCAR2 at millimolar concentrations in the study of receptor signaling in human colonic cells.

Restoring GPR109A expression in human colon cancer cells enabled apoptosis in the presence of butyrate or nicotinate; the receptor-mediated response did not require histone deacetylation inhibition.

Butyrate promoted Aldh1a1 and Il10 expression in mouse dendritic/macrophage experiments through Gpr109a signaling.

The retinoic-acid-receptor antagonist LE135 abolished the increased Treg conversion induced by butyrate- or niacin-treated wild-type mouse dendritic cells.

Butyrate-induced Il18 expression in mouse colonic epithelium required Gpr109a/Hcar2.

Differentiating human blood monocytes with butyrate enhanced subsequent macrophage antibacterial activity without increasing inflammatory cytokine output.

HDAC3 inhibition and HDAC3 siRNA supported the HDAC3-dependent differentiation program induced by butyrate in human macrophages.

Butyrate-differentiated macrophages showed reduced mTOR activity, increased LC3-associated defense and antimicrobial peptide expression alongside metabolic remodeling.

Butyrate reduced TNF and IL-6 secretion by more than 50% in ex-vivo inflamed human IBD biopsies.

Butyrate restored MCT1 and IL-18 expression in challenged human epithelial organoids, but did not suppress their pro-inflammatory gene expression as it did in mononuclear-cell experiments.

GPR109A/G-protein inhibition did not remove the tested human monocyte/macrophage anti-inflammatory response to butyrate; HDAC3-related mechanisms were implicated.

Butyrate exposure during human monocyte differentiation increased S100A8/S100A9 expression and calprotectin protein in the resulting macrophages.

Combined S100A8/S100A9 siRNA increased the intracellular bacterial load in butyrate-differentiated human macrophages.

Butyrate expanded gut and bone-marrow Tregs; their interaction with CD8 T cells increased Wnt10b production and bone formation in young mice.

Tregs promoted NFAT1-SMAD3 complex assembly in mouse CD8 cells, driving Wnt10b expression in the butyrate-associated bone pathway.

Reconstituting TCR-beta-deficient mice with Wnt10b-deficient CD8 T cells prevented butyrate-induced bone formation and mass acquisition; lowering Treg numbers also prevented the response.

Butyrate and propionate shifted osteoclast metabolism toward glycolysis, reduced Traf6/Nfatc1 expression and suppressed osteoclast differentiation in the reported experiments.

Antibiotic-depleted or germ-free female mice lost the bone-anabolic response to intermittent PTH; restoring physiological butyrate levels restored the response.

The permissive butyrate response involved GPR43 signaling in dendritic cells and GPR43-independent effects in T cells in the PTH study.

Butyrate activated human GPR43/FFAR2 in the receptor-deorphanization assays.

Butyrate was an agonist at human GPR41/FFAR3, whose chain-length preference differed from GPR43.

Butyrate activated intestinal gluconeogenic gene expression through a cAMP-dependent mechanism in the rodent study.

Mice deficient in intestinal gluconeogenesis lost the weight/glucose benefits of SCFA or soluble-fiber interventions despite similar microbial-composition changes.

Butyrate administration induced GLP-1/GIP responses and reduced food intake in the mouse study.

Ffar3-deficient mice retained the body-weight and food-intake effects of butyrate; FFAR3 had only a minor role in the GLP-1 response and was unnecessary for GIP induction.

Feeding sodium butyrate at 5% of a high-fat diet increased thermogenesis and mitochondrial adaptation in mouse muscle and brown fat, with increased PGC-1alpha expression and insulin sensitivity.

In nine lean men, four weeks of 4 g/day oral sodium butyrate was associated with improved peripheral and hepatic insulin sensitivity.

The same 4 g/day, four-week pilot found no insulin-sensitivity improvement in its ten men with metabolic syndrome.

Oral sodium butyrate did not significantly increase brown-adipose glucose uptake in either lean or metabolic-syndrome men in the pilot.

In 23 hypertensive adults, 3.9 g/day oral sodium butyrate for four weeks increased daytime systolic pressure by 9.63 mmHg and diastolic pressure by 5.08 mmHg versus sodium-matched placebo.

Ten Black adults with stage-1 hypertension had lower daytime systolic pressure after an acute 80 mM butyrate enema in a crossover comparison with a 5 mM low-dose enema.

Oral butyrate increased plasma butyrate without increasing fecal butyrate in the hypertension trial.

Sodium butyrate reduced proteinuria, podocyte loss and renal injury in the mouse Adriamycin-nephropathy study.

Hcar2-deficient mice lost the reported protective response to butyrate in Adriamycin nephropathy.

Post-training sodium butyrate injection enabled 24-hour object-location memory after otherwise subthreshold training in mice, with increased hippocampal Bdnf transcripts.

Hippocampal Bdnf siRNA blocked the memory-enabling effect of post-training sodium butyrate in the mouse task.

Carbohydrate-derived microbial metabolites including butyrate fueled hyperproliferation of Msh2-deficient colonic epithelium in the Apc-mutant mouse cancer model.

Higher circulating butyrate and propionate were associated with resistance to CTLA-4 blockade in the human cancer cohorts.

Butyrate exposure limited anti-CTLA-4 antitumor activity in the mouse experiments.