{"id":"7485f458-8184-5e31-a76c-ba47da528804","stable_key":"8b3cf083-ea9c-54f5-b42b-bf1fef5b2978:metformin-gudca-fxr","predicate":"inhibits","statement":"GUDCA was identified as an intestinal FXR antagonist, and these changes were accompanied by inhibition of intestinal FXR signalling.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"1491c04e-91f4-51df-890b-372bcd81a72e","mechanism_event_label":"That bile acid switches off a gut receptor that controls metabolism.","subject":{"id":"41706e0b-b327-5545-8506-dcaf0e7125b8","slug":"gudca","display_name":"Glycoursodeoxycholic acid / GUDCA","entity_type_key":"small_molecule"},"object":{"id":"b01328ab-2538-5515-ab2b-0ccee393ae81","slug":"intestinal-fxr-signaling","display_name":"Intestinal farnesoid X receptor signalling","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"1491c04e-91f4-51df-890b-372bcd81a72e","stable_key":"8b3cf083-ea9c-54f5-b42b-bf1fef5b2978:metformin-gudca-fxr-event","event_type":"biochemical_relationship","label":"That bile acid switches off a gut receptor that controls metabolism.","description":"GUDCA was identified as an intestinal FXR antagonist, and these changes were accompanied by inhibition of intestinal FXR signalling.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"fcb53473-c0bd-5e70-891f-ab3b48353d25","slug":"nr1h4","display_name":"Human farnesoid X receptor / NR1H4","entity_type_key":"protein"},"role":"antagonised_receptor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"41706e0b-b327-5545-8506-dcaf0e7125b8","slug":"gudca","display_name":"Glycoursodeoxycholic acid / GUDCA","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"b01328ab-2538-5515-ab2b-0ccee393ae81","slug":"intestinal-fxr-signaling","display_name":"Intestinal farnesoid X receptor signalling","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/metformin-research/30397356.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"0dbf1f5a262207595ede745deeb9fc79ba7732dc4d6af6b5c9d654712d79c1cf\", \"start_char\": 0, \"end_char\": 1433, \"text_sha256\": \"0dbf1f5a262207595ede745deeb9fc79ba7732dc4d6af6b5c9d654712d79c1cf\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Metagenomic and metabolomic analysis in newly diagnosed type 2 diabetes with mouse colonisation experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Three days of metformin in treatment-naive people; B. fragilis colonisation in high-fat-diet mice","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"A three-day human exposure with a mouse causal test. GUDCA is identified as an intestinal FXR antagonist; whole-body FXR biology is not claimed.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake.","comparator":null,"unit":null,"notes":"","entity":{"slug":"metformin","display_name":"Metformin","entity_type_key":"drug"}},{"dimension":"organism","value_text":"Human and mouse","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"That bile acid switches off a gut receptor that controls metabolism.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[metformin-p30397356] Gut microbiota and intestinal FXR mediate the clinical benefits of metformin. (2018). https://pubmed.ncbi.nlm.nih.gov/30397356/ DOI: 10.1038/s41591-018-0222-4","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Gut lumen and intestinal epithelium","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"183a10eb-7cac-5a84-b607-bc6cfbc24627","evidence_kind":"source_excerpt","locator":"Lines 879-890","start_line":879,"end_line":890,"excerpt":"### metformin-gudca-fxr\nGUDCA was identified as an intestinal FXR antagonist, and these changes were accompanied by inhibition of intestinal FXR signalling.\nCondition category: normal\nnutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake.\nplain_language: That bile acid switches off a gut receptor that controls metabolism.\norganism: Human and mouse\ntissue_or_cell_type: Gut lumen and intestinal epithelium\nexperimental_model: Metagenomic and metabolomic analysis in newly diagnosed type 2 diabetes with mouse colonisation experiments\nlimitations: A three-day human exposure with a mouse causal test. GUDCA is identified as an intestinal FXR antagonist; whole-body FXR biology is not claimed.\nexposure: Three days of metformin in treatment-naive people; B. fragilis colonisation in high-fat-diet mice\nevidence_span: {\"source_cache\": \"artifacts/metformin-research/30397356.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"0dbf1f5a262207595ede745deeb9fc79ba7732dc4d6af6b5c9d654712d79c1cf\", \"start_char\": 0, \"end_char\": 1433, \"text_sha256\": \"0dbf1f5a262207595ede745deeb9fc79ba7732dc4d6af6b5c9d654712d79c1cf\"}\n[metformin-p30397356] Gut microbiota and intestinal FXR mediate the clinical benefits of metformin. (2018). https://pubmed.ncbi.nlm.nih.gov/30397356/ DOI: 10.1038/s41591-018-0222-4","model_system":"Metagenomic and metabolomic analysis in newly diagnosed type 2 diabetes with mouse colonisation experiments","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [metformin-p30397356] Gut microbiota and intestinal FXR mediate the clinical benefits of metformin. (2018). https://pubmed.ncbi.nlm.nih.gov/30397356/ DOI: 10.1038/s41591-018-0222-4","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"d0474bd9-7cfd-5695-a152-12f3633a6813","stable_key":"import-8b3cf083-ea9c-54f5-b42b-bf1fef5b2978","title":"Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"0b51d0759aeeb88ac5b3a6277245a196b2bb024d7c32ec89379ed428fb06bfb5","revision_id":"0405c75e-f06e-5af7-a642-1777802f6004","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}