{"id":"4eb181b5-8b09-5c71-8d9f-fa1cf1b82041","stable_key":"8b3cf083-ea9c-54f5-b42b-bf1fef5b2978:metformin-microbial-metalloproteins","predicate":"alters","statement":"In a gut simulator, many of the metformin-regulated genes in species from two different phyla encoded metalloproteins or metal transporters.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"e82acac4-6feb-522f-8881-32e4ed14fef8","mechanism_event_label":"The genes the drug touched in bacteria were unusually often metal-handling genes.","subject":{"id":"519971b1-5aef-5ad7-8022-840144855cd0","slug":"metformin","display_name":"Metformin","entity_type_key":"drug"},"object":{"id":"4d9c823e-92f8-5a6f-b675-6207907f58fc","slug":"gut-microbiota-composition","display_name":"Gut microbiota composition","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"e82acac4-6feb-522f-8881-32e4ed14fef8","stable_key":"8b3cf083-ea9c-54f5-b42b-bf1fef5b2978:metformin-microbial-metalloproteins-event","event_type":"observed_intervention","label":"The genes the drug touched in bacteria were unusually often metal-handling genes.","description":"In a gut simulator, many of the metformin-regulated genes in species from two different phyla encoded metalloproteins or metal transporters.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"2a870bb5-05a0-5e51-a70c-a9a843a8b571","slug":"copper-ii","display_name":"Copper(II) ion","entity_type_key":"ion"},"role":"candidate_metal","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"519971b1-5aef-5ad7-8022-840144855cd0","slug":"metformin","display_name":"Metformin","entity_type_key":"drug"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"4d9c823e-92f8-5a6f-b675-6207907f58fc","slug":"gut-microbiota-composition","display_name":"Gut microbiota composition","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/28530702.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"885eedb24772fbd218ff6497da6c39f486d0e0b0293ddd97e8fd7b3f23330b11\", \"start_char\": 0, \"end_char\": 1137, \"text_sha256\": \"885eedb24772fbd218ff6497da6c39f486d0e0b0293ddd97e8fd7b3f23330b11\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Four-month double-blind randomised trial with faecal transfer to germ-free mice and a gut simulator","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Metformin or placebo for 4 months in treatment-naive type 2 diabetes","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The faecal transfer carries the causal claim. The metalloprotein observation is a genomic annotation, not a measured metal interaction.","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":"The genes the drug touched in bacteria were unusually often metal-handling genes.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[metformin-p28530702] Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug. (2017). https://pubmed.ncbi.nlm.nih.gov/28530702/ DOI: 10.1038/nm.4345","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Gut microbiome","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"d08ad5df-d64b-52ec-8239-46cf06752dc2","evidence_kind":"source_excerpt","locator":"Lines 931-942","start_line":931,"end_line":942,"excerpt":"### metformin-microbial-metalloproteins\nIn a gut simulator, many of the metformin-regulated genes in species from two different phyla encoded metalloproteins or metal transporters.\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: The genes the drug touched in bacteria were unusually often metal-handling genes.\norganism: Human and mouse\ntissue_or_cell_type: Gut microbiome\nexperimental_model: Four-month double-blind randomised trial with faecal transfer to germ-free mice and a gut simulator\nlimitations: The faecal transfer carries the causal claim. The metalloprotein observation is a genomic annotation, not a measured metal interaction.\nexposure: Metformin or placebo for 4 months in treatment-naive type 2 diabetes\nevidence_span: {\"source_cache\": \"artifacts/metformin-research/28530702.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"885eedb24772fbd218ff6497da6c39f486d0e0b0293ddd97e8fd7b3f23330b11\", \"start_char\": 0, \"end_char\": 1137, \"text_sha256\": \"885eedb24772fbd218ff6497da6c39f486d0e0b0293ddd97e8fd7b3f23330b11\"}\n[metformin-p28530702] Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug. 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