Butyrate

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

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

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.

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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

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

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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

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

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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

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

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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

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

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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

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

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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

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

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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

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

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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

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

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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

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

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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

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

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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

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

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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

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

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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

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.

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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

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

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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

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

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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

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

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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

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

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

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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

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

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

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

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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

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

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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

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

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

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

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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

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

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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

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

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

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

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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

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

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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

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

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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

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

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

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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

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

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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

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

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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

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

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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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

evidence_span

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experimental_model

Murine tumour models with selective bacterial expansion and metabolomics, plus a human cohort and a human intervention study

exposure

Oat beta-glucan with anti-PD-1 checkpoint blockade in mice, and oat beta-glucan supplementation in people

limitations

The causal efficacy claim is demonstrated in mice. The human components are a correlation in a colorectal cancer cohort and an intervention study reporting safety and metabolite change, so no anticancer benefit in people is established here.

nutrient_topic

Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. · Beta-glucan

organism

Mouse

plain_language

The cereal glucan never touches the tumour; it feeds a gut bacterium whose products wake the cells that do.

primary_references

[bg-p42214334] Oat-β-glucan potentiates anti-PD-1 efficacy through Faecalibacterium prausnitzii-derived butyrate and indole-3-propionic acid. (2026). https://pubmed.ncbi.nlm.nih.gov/42214334/ DOI: 10.1016/j.chom.2026.05.002

tissue_or_cell_type

Gut microbiota and tumour microenvironment

Beta-glucan: a structural family rather than an agent, what decides whether a bound glucan actually signals, the complement route that a cereal and a yeast preparation share, and the unequal human evidence behind each (2026-09-22) · lines 658–669

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Murine tumour models with selective bacterial expansion and metabolomics, plus a human cohort and a human intervention study · source_derived_draft · unverified_draft

### bg-a-cereal-glucan-reaches-immunity Oat-beta-glucan enhances anti-PD-1 efficacy in murine models by selectively expanding Faecalibacterium prausnitzii, combining anti-PD-1 with either oat-beta-glucan or F. prausnitzii boosts intratumoral dendritic cell and CD8+ T cell infiltration and cytotoxic activation compared with anti-PD-1 monotherapy, metabolomics identifies F. prausnitzii-derived butyrate and indole-3-propionic acid as key mediators with butyrate activating dendritic cells via the HDAC8, H3K27ac and NF-kappa-B p65 pathway, in a colorectal cancer cohort undergoing anti-PD-1 treatment higher baseline F. prausnitzii abundance and elevated plasma butyrate and indole-3-propionic acid correlate with improved responses, and a human intervention study confirms oat-beta-glucan safety, its ability to increase butyrate and indole-3-propionic acid, and its capacity to modulate F. prausnitzii. Condition category: normal nutrient_topic: Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. plain_language: The cereal glucan never touches the tumour; it feeds a gut bacterium whose products wake the cells that do. organism: Mouse tissue_or_cell_type: Gut microbiota and tumour microenvironment experimental_model: Murine tumour models with selective bacterial expansion and metabolomics, plus a human cohort and a human intervention study limitations: The causal efficacy claim is demonstrated in mice. The human components are a correlation in a colorectal cancer cohort and an intervention study reporting safety and metabolite change, so no anticancer benefit in people is established here. exposure: Oat beta-glucan with anti-PD-1 checkpoint blockade in mice, and oat beta-glucan supplementation in people evidence_span: {"source_cache": "artifacts/glucan-research/42214334.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1e145fb1c4163d9e0cd10a4055b68fa47de521dcf19d25253d42fc9c971d56ba", "start_char": 0, "end_char": 1310, "text_sha256": "1e145fb1c4163d9e0cd10a4055b68fa47de521dcf19d25253d42fc9c971d56ba"} [bg-p42214334] Oat-β-glucan potentiates anti-PD-1 efficacy through Faecalibacterium prausnitzii-derived butyrate and indole-3-propionic acid. (2026). https://pubmed.ncbi.nlm.nih.gov/42214334/ DOI: 10.1016/j.chom.2026.05.002

evidence_span

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experimental_model

Fixed-sequence crossover intervention with three granolas over three days each

exposure

Granola containing low, medium or high cereal beta-glucan, given in that order

limitations

Fourteen completers, a fixed sequence rather than randomised order, and granolas that differed in other constituents including inulin. Short-chain fatty acids were measured in blood while faecal samples were used for the microbiota.

nutrient_topic

Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. · Beta-glucan

organism

Human

plain_language

Three days of a cereal glucan raised two of the three main fermentation acids in the blood.

primary_references

[bg-p35578615] A Three-Day Intervention With Granola Containing Cereal Beta-Glucan Improves Glycemic Response and Changes the Gut Microbiota in Healthy Individuals: A Crossover Study. (2022). https://pubmed.ncbi.nlm.nih.gov/35578615/ DOI: 10.3389/fnut.2022.796362

tissue_or_cell_type

Blood and faecal microbiota

Beta-glucan: a structural family rather than an agent, what decides whether a bound glucan actually signals, the complement route that a cereal and a yeast preparation share, and the unequal human evidence behind each (2026-09-22) · lines 645–656

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Fixed-sequence crossover intervention with three granolas over three days each · source_derived_draft · unverified_draft

### bg-circulating-scfa-rise-with-granola A three-day intervention with granola containing cereal beta-glucan improved the glycemic response and changed the gut microbiota, with circulating acetate and butyrate increasing while propionate did not, in a study in which participants consumed granolas of differing beta-glucan content in fixed sequence and in which the granolas also differed in other constituents. Condition category: normal nutrient_topic: Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. plain_language: Three days of a cereal glucan raised two of the three main fermentation acids in the blood. organism: Human tissue_or_cell_type: Blood and faecal microbiota experimental_model: Fixed-sequence crossover intervention with three granolas over three days each limitations: Fourteen completers, a fixed sequence rather than randomised order, and granolas that differed in other constituents including inulin. Short-chain fatty acids were measured in blood while faecal samples were used for the microbiota. exposure: Granola containing low, medium or high cereal beta-glucan, given in that order evidence_span: {"source_cache": "artifacts/glucan-research/35578615.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "df79afd1ef3d79ffee2a9da5f5f7e487f296cca7e9ccfcda177266b08efed747", "start_char": 0, "end_char": 2197, "text_sha256": "df79afd1ef3d79ffee2a9da5f5f7e487f296cca7e9ccfcda177266b08efed747"} [bg-p35578615] A Three-Day Intervention With Granola Containing Cereal Beta-Glucan Improves Glycemic Response and Changes the Gut Microbiota in Healthy Individuals: A Crossover Study. (2022). https://pubmed.ncbi.nlm.nih.gov/35578615/ DOI: 10.3389/fnut.2022.796362

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

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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

evidence_span

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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

Each bacterial enzyme family is recorded independently; species and isoform remain unresolved.

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 1052–1063

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-bct The study reported increased bacterial butyryl-CoA:acetate-CoA transferase in the pathway associated with increased butyrate production. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Each bacterial enzyme family is recorded independently; species and isoform remain unresolved. 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

evidence_span

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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

Each bacterial enzyme family is recorded independently; species and isoform remain unresolved.

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 1039–1050

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-buk The study reported increased bacterial butyrate kinase in the pathway associated with increased butyrate production. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Each bacterial enzyme family is recorded independently; species and isoform remain unresolved. 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

evidence_span

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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

evidence_span

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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

Each bacterial enzyme family is recorded independently; species and isoform remain unresolved.

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 1026–1037

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-ptb The study reported increased bacterial phosphotransbutyrylase in the pathway associated with increased butyrate production. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Each bacterial enzyme family is recorded independently; species and isoform remain unresolved. 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

evidence_access

Primary abstract

experimental_model

Twelve-week rat supplementation study with fecal transplantation.

limitations

Taxa or fecal concentration do not alone establish production flux, a specific strain enzyme, or butyrate as the sole mediator.

nutrient_topic

Myricetin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Myricetin

plain_language

Gut effects may help explain activity despite limited systemic exposure.

primary_references

Myricetin supplementation decreases hepatic lipid synthesis and inflammation by modulating gut microbiota. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34469716/ · DOI 10.1016/j.celrep.2021.109641

Myricetin: metabolism, immune signaling, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 540–546

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Twelve-week rat supplementation study with fecal transplantation. · source_derived_draft · unverified_draft

## myricetin-rat-butyrate Gut effects may help explain activity despite limited systemic exposure. Myricetin altered butyrate-associated gut microbial composition alongside reduced hepatic lipid synthesis and inflammation in high-fat-fed rats. Model: Twelve-week rat supplementation study with fecal transplantation. Limitations: Taxa or fecal concentration do not alone establish production flux, a specific strain enzyme, or butyrate as the sole mediator. Evidence access: Primary abstract Myricetin supplementation decreases hepatic lipid synthesis and inflammation by modulating gut microbiota. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34469716/ · DOI 10.1016/j.celrep.2021.109641

evidence_span

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experimental_model

Ligand bank screening in yeast, confirmed by calcium mobilisation, GTP-gamma-S binding and oocyte coexpression

exposure

Short chain carboxylic acid anions applied to recombinant GPR41 and GPR43

limitations

The deorphanising paper. Potencies come from recombinant systems, not from tissue, and the authors state plainly that the cognate physiological ligands are not clear.

nutrient_topic

Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion. · Acetic acid

organism

Human and mouse receptors

plain_language

Acetate is not only fuel; it is the signal that identified this receptor.

primary_references

[acetate-p12496283] 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

tissue_or_cell_type

Transfected mammalian cells and Xenopus oocytes

Acetic acid: the ingested acid, the receptors acetate binds, the acetyl-CoA it becomes, and the acetyl groups that reach histones (2026-09-21) · lines 225–236

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ligand bank screening in yeast, confirmed by calcium mobilisation, GTP-gamma-S binding and oocyte coexpression · source_derived_draft · unverified_draft

### acetate-acetate-activates-ffar2 The acetate anion was identified as an agonist of human GPR43 during ligand bank screening in yeast and confirmed after transient transfection using calcium mobilisation and GTP-gamma-S binding assays and by coexpression with GIRK potassium channels in Xenopus oocytes, with formate, propionate, butyrate and pentanoate also showing agonist activity. Condition category: normal nutrient_topic: Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion. plain_language: Acetate is not only fuel; it is the signal that identified this receptor. organism: Human and mouse receptors tissue_or_cell_type: Transfected mammalian cells and Xenopus oocytes experimental_model: Ligand bank screening in yeast, confirmed by calcium mobilisation, GTP-gamma-S binding and oocyte coexpression limitations: The deorphanising paper. Potencies come from recombinant systems, not from tissue, and the authors state plainly that the cognate physiological ligands are not clear. exposure: Short chain carboxylic acid anions applied to recombinant GPR41 and GPR43 evidence_span: {"source_cache": "artifacts/acetate-research/12496283.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "83f7777cab02a7c69f063d21e26f895884724f46ad539ebc767d9e6f371bf64f", "start_char": 0, "end_char": 1291, "text_sha256": "83f7777cab02a7c69f063d21e26f895884724f46ad539ebc767d9e6f371bf64f"} [acetate-p12496283] 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

evidence_span

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experimental_model

Isolated perfused rat colon with luminal and vascular short-chain fatty acid infusion and receptor pharmacology

exposure

Acetate, propionate and butyrate perfused luminally or vascularly, with FFAR2/FFAR3 agonists, an FFAR3 antagonist, nifedipine, diazoxide and 2,4-dinitrophenol

limitations

An isolated organ preparation with an intact blood supply. It reaches the opposite mechanistic conclusion from the knockout work in this collection and is why the receptor route is recorded as disputed.

nutrient_topic

Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion. · Acetic acid

organism

Rat

plain_language

Acetate and butyrate released the hormone from the isolated gut; propionate did not.

primary_references

[acetate-p29494208] The impact of short-chain fatty acids on GLP-1 and PYY secretion from the isolated perfused rat colon. (2018). https://pubmed.ncbi.nlm.nih.gov/29494208/ DOI: 10.1152/ajpgi.00346.2017

tissue_or_cell_type

Colon

Acetic acid: the ingested acid, the receptors acetate binds, the acetyl-CoA it becomes, and the acetyl groups that reach histones (2026-09-21) · lines 329–340

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isolated perfused rat colon with luminal and vascular short-chain fatty acid infusion and receptor pharmacology · source_derived_draft · unverified_draft

### acetate-acetate-glp1-perfused Luminal and especially vascular infusion of acetate and butyrate significantly increased colonic GLP-1 secretion and to a minor extent PYY secretion in the isolated perfused rat colon, but only after enhancement of intracellular cAMP, while propionate affected neither GLP-1 nor PYY by either route. Condition category: normal nutrient_topic: Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion. plain_language: Acetate and butyrate released the hormone from the isolated gut; propionate did not. organism: Rat tissue_or_cell_type: Colon experimental_model: Isolated perfused rat colon with luminal and vascular short-chain fatty acid infusion and receptor pharmacology limitations: An isolated organ preparation with an intact blood supply. It reaches the opposite mechanistic conclusion from the knockout work in this collection and is why the receptor route is recorded as disputed. exposure: Acetate, propionate and butyrate perfused luminally or vascularly, with FFAR2/FFAR3 agonists, an FFAR3 antagonist, nifedipine, diazoxide and 2,4-dinitrophenol evidence_span: {"source_cache": "artifacts/acetate-research/29494208.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9f8def7b832fdd5d5aed67891c84b18b597d558d9361a92412ccc44264b88126", "start_char": 0, "end_char": 2445, "text_sha256": "9f8def7b832fdd5d5aed67891c84b18b597d558d9361a92412ccc44264b88126"} [acetate-p29494208] The impact of short-chain fatty acids on GLP-1 and PYY secretion from the isolated perfused rat colon. (2018). https://pubmed.ncbi.nlm.nih.gov/29494208/ DOI: 10.1152/ajpgi.00346.2017

evidence_span

{"source_cache": "artifacts/acetate-research/27966553.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "25ef476e62dd28f354099501d2919c3f765aaddd89d1a05739e3e0dc703d11ac", "start_char": 0, "end_char": 1363, "text_sha256": "25ef476e62dd28f354099501d2919c3f765aaddd89d1a05739e3e0dc703d11ac"}

experimental_model

GPR43 knockout mice with B-cell and dendritic-cell coculture and retinoic acid signalling blockade

exposure

Dietary acetate or butyrate in wild-type and GPR43 knockout mice, with in vitro IgA class switching assays

limitations

A clean set of controls: butyrate did not substitute for acetate, the effect was independent of T cells, and blocking the downstream vitamin A metabolite removed it.

nutrient_topic

Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion. · Acetic acid

organism

Mouse

plain_language

Acetate tells the gut to make the antibody that coats its own bacteria, and butyrate does not stand in for it.

primary_references

[acetate-p27966553] Microbiota metabolite short-chain fatty acid acetate promotes intestinal IgA response to microbiota which is mediated by GPR43. (2017). https://pubmed.ncbi.nlm.nih.gov/27966553/ DOI: 10.1038/mi.2016.114

tissue_or_cell_type

Intestinal mucosa

Acetic acid: the ingested acid, the receptors acetate binds, the acetyl-CoA it becomes, and the acetyl groups that reach histones (2026-09-21) · lines 381–392

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · GPR43 knockout mice with B-cell and dendritic-cell coculture and retinoic acid signalling blockade · source_derived_draft · unverified_draft

### acetate-acetate-iga GPR43 knockout mice had lower levels of intestinal IgA and of IgA-coated gut bacteria than wild-type mice, and feeding wild-type but not GPR43 knockout mice acetate, but not butyrate, promoted the intestinal IgA response independently of T cells. Condition category: normal nutrient_topic: Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion. plain_language: Acetate tells the gut to make the antibody that coats its own bacteria, and butyrate does not stand in for it. organism: Mouse tissue_or_cell_type: Intestinal mucosa experimental_model: GPR43 knockout mice with B-cell and dendritic-cell coculture and retinoic acid signalling blockade limitations: A clean set of controls: butyrate did not substitute for acetate, the effect was independent of T cells, and blocking the downstream vitamin A metabolite removed it. exposure: Dietary acetate or butyrate in wild-type and GPR43 knockout mice, with in vitro IgA class switching assays evidence_span: {"source_cache": "artifacts/acetate-research/27966553.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "25ef476e62dd28f354099501d2919c3f765aaddd89d1a05739e3e0dc703d11ac", "start_char": 0, "end_char": 1363, "text_sha256": "25ef476e62dd28f354099501d2919c3f765aaddd89d1a05739e3e0dc703d11ac"} [acetate-p27966553] Microbiota metabolite short-chain fatty acid acetate promotes intestinal IgA response to microbiota which is mediated by GPR43. (2017). https://pubmed.ncbi.nlm.nih.gov/27966553/ DOI: 10.1038/mi.2016.114

evidence_span

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experimental_model

Rat colonic epithelial cells with competing labelled substrates and ATP-citrate lyase inhibition

exposure

Labelled acetate, propionate, butyrate, 3-hydroxybutyrate, glucose and glutamine, with hydroxycitrate as an ATP-citrate lyase inhibitor

limitations

An isolated cell measurement. Its ATP-citrate lyase result anticipates by seventeen years the in vivo finding in this collection that lipogenic acetyl-CoA can arrive without that enzyme.

nutrient_topic

Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion. · Acetic acid

organism

Rat

plain_language

The cells lining the colon build their membranes mostly out of acetate, not out of glucose.

primary_references

[acetate-p14608066] Acetate and butyrate are the major substrates for de novo lipogenesis in rat colonic epithelial cells. (2003). https://pubmed.ncbi.nlm.nih.gov/14608066/ DOI: 10.1093/jn/133.11.3509

tissue_or_cell_type

Colonic epithelium

Acetic acid: the ingested acid, the receptors acetate binds, the acetyl-CoA it becomes, and the acetyl groups that reach histones (2026-09-21) · lines 524–535

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat colonic epithelial cells with competing labelled substrates and ATP-citrate lyase inhibition · source_derived_draft · unverified_draft

### acetate-colonocyte-prefers-acetate Acetate made a significantly larger carbon contribution to lipids than propionate, butyrate, glucose or glutamine in rat colonic epithelial cells, with butyrate and 3-hydroxybutyrate the other major contributors and glucose, glutamine and propionate making only minor contributions, and incorporation was significantly greater into phospholipids than into free fatty acids and triacylglycerides, suggesting the major role of this lipogenesis is membrane synthesis. Condition category: normal nutrient_topic: Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion. plain_language: The cells lining the colon build their membranes mostly out of acetate, not out of glucose. organism: Rat tissue_or_cell_type: Colonic epithelium experimental_model: Rat colonic epithelial cells with competing labelled substrates and ATP-citrate lyase inhibition limitations: An isolated cell measurement. Its ATP-citrate lyase result anticipates by seventeen years the in vivo finding in this collection that lipogenic acetyl-CoA can arrive without that enzyme. exposure: Labelled acetate, propionate, butyrate, 3-hydroxybutyrate, glucose and glutamine, with hydroxycitrate as an ATP-citrate lyase inhibitor evidence_span: {"source_cache": "artifacts/acetate-research/14608066.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b2c891f60d02b85a8f4e87f26751f1129b0445fe52fb35ca5e5e20a92d4ecc5a", "start_char": 0, "end_char": 1642, "text_sha256": "b2c891f60d02b85a8f4e87f26751f1129b0445fe52fb35ca5e5e20a92d4ecc5a"} [acetate-p14608066] Acetate and butyrate are the major substrates for de novo lipogenesis in rat colonic epithelial cells. (2003). https://pubmed.ncbi.nlm.nih.gov/14608066/ DOI: 10.1093/jn/133.11.3509

evidence_span

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experimental_model

Isolated perfused rat colon with luminal and vascular short-chain fatty acid infusion and receptor pharmacology

exposure

Acetate, propionate and butyrate perfused luminally or vascularly, with FFAR2/FFAR3 agonists, an FFAR3 antagonist, nifedipine, diazoxide and 2,4-dinitrophenol

limitations

An isolated organ preparation with an intact blood supply. It reaches the opposite mechanistic conclusion from the knockout work in this collection and is why the receptor route is recorded as disputed.

nutrient_topic

Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion. · Acetic acid

organism

Rat

plain_language

The natural fatty acids are weak at this receptor; a synthetic drug is hundreds of times stronger.

primary_references

[acetate-p29494208] The impact of short-chain fatty acids on GLP-1 and PYY secretion from the isolated perfused rat colon. (2018). https://pubmed.ncbi.nlm.nih.gov/29494208/ DOI: 10.1152/ajpgi.00346.2017

tissue_or_cell_type

Colon

Acetic acid: the ingested acid, the receptors acetate binds, the acetyl-CoA it becomes, and the acetyl groups that reach histones (2026-09-21) · lines 355–366

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isolated perfused rat colon with luminal and vascular short-chain fatty acid infusion and receptor pharmacology · source_derived_draft · unverified_draft

### acetate-weak-partial-agonism Receptor studies confirmed acetate, propionate and butyrate to be low-potency partial agonists of FFAR2 compared with the synthetic agonist CFMB, which is a full agonist with roughly 750-fold higher potency than the short-chain fatty acids. Condition category: normal nutrient_topic: Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion. plain_language: The natural fatty acids are weak at this receptor; a synthetic drug is hundreds of times stronger. organism: Rat tissue_or_cell_type: Colon experimental_model: Isolated perfused rat colon with luminal and vascular short-chain fatty acid infusion and receptor pharmacology limitations: An isolated organ preparation with an intact blood supply. It reaches the opposite mechanistic conclusion from the knockout work in this collection and is why the receptor route is recorded as disputed. exposure: Acetate, propionate and butyrate perfused luminally or vascularly, with FFAR2/FFAR3 agonists, an FFAR3 antagonist, nifedipine, diazoxide and 2,4-dinitrophenol evidence_span: {"source_cache": "artifacts/acetate-research/29494208.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9f8def7b832fdd5d5aed67891c84b18b597d558d9361a92412ccc44264b88126", "start_char": 0, "end_char": 2445, "text_sha256": "9f8def7b832fdd5d5aed67891c84b18b597d558d9361a92412ccc44264b88126"} [acetate-p29494208] The impact of short-chain fatty acids on GLP-1 and PYY secretion from the isolated perfused rat colon. (2018). https://pubmed.ncbi.nlm.nih.gov/29494208/ DOI: 10.1152/ajpgi.00346.2017