{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T01:43:53Z","timestamp":1782870233890,"version":"3.54.5"},"reference-count":52,"publisher":"Elsevier BV","issue":"11","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T00:00:00Z","timestamp":1761436800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007452","name":"Wu Jieping Medical Foundation","doi-asserted-by":"publisher","award":["320.6750.2023-3-16"],"award-info":[{"award-number":["320.6750.2023-3-16"]}],"id":[{"id":"10.13039\/100007452","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U24A20789"],"award-info":[{"award-number":["U24A20789"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82130112"],"award-info":[{"award-number":["82130112"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82404946"],"award-info":[{"award-number":["82404946"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82204699"],"award-info":[{"award-number":["82204699"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["iScience"],"published-print":{"date-parts":[[2025,11]]},"DOI":"10.1016\/j.isci.2025.113892","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:11:57Z","timestamp":1761696717000},"page":"113892","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"title":["Roseburia hominis enriched by baicalin reverses the non-response to metformin via upregulating linolenic acid metabolism"],"prefix":"10.1016","volume":"28","author":[{"given":"Zenghui","family":"Miao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianglan","family":"Long","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bangrong","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2985-3798","authenticated-orcid":false,"given":"Dan","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiting","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.isci.2025.113892_bib1","doi-asserted-by":"crossref","first-page":"3789","DOI":"10.1016\/j.cell.2024.06.029","article-title":"Diabetes mellitus-progress and opportunities in the evolving epidemic","volume":"187","author":"Abel","year":"2024","journal-title":"Cell"},{"key":"10.1016\/j.isci.2025.113892_bib2","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1007\/s00125-017-4352-x","article-title":"The effects of metformin on gut microbiota and the immune system as research frontiers","volume":"60","author":"Pollak","year":"2017","journal-title":"Diabetologia"},{"key":"10.1016\/j.isci.2025.113892_bib3","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.1210\/clinem\/dgac759","article-title":"Predictors of metformin failure: repurposing electronic health record data to identify high-risk patients","volume":"108","author":"Bielinski","year":"2023","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"10.1016\/j.isci.2025.113892_bib4","doi-asserted-by":"crossref","first-page":"501","DOI":"10.2337\/dc09-1749","article-title":"Secondary failure of metformin monotherapy in clinical practice","volume":"33","author":"Brown","year":"2010","journal-title":"Diabetes Care"},{"key":"10.1016\/j.isci.2025.113892_bib5","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1111\/j.1464-5491.2007.02078.x","article-title":"Initial monotherapy with either metformin or sulphonylureas often fails to achieve or maintain current glycaemic goals in patients with Type 2 diabetes in UK primary care","volume":"24","author":"Cook","year":"2007","journal-title":"Diabet. Med."},{"key":"10.1016\/j.isci.2025.113892_bib6","doi-asserted-by":"crossref","first-page":"2427","DOI":"10.1056\/NEJMoa066224","article-title":"Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy","volume":"355","author":"Kahn","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.isci.2025.113892_bib7","first-page":"302","article-title":"Pharmacogenetic studies update in type 2 diabetes mellitus","volume":"7","author":"Singh","year":"2016","journal-title":"Diabetes"},{"key":"10.1016\/j.isci.2025.113892_bib8","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1007\/s40618-022-01989-y","article-title":"Implications of genetic variations, differential gene expression, and allele-specific expression on metformin response in drug-na\u00efve type 2 diabetes","volume":"46","author":"Vohra","year":"2023","journal-title":"J. Endocrinol. Investig."},{"key":"10.1016\/j.isci.2025.113892_bib9","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/s41579-020-0433-9","article-title":"Gut microbiota in human metabolic health and disease","volume":"19","author":"Fan","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"10.1016\/j.isci.2025.113892_bib10","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/j.cmet.2020.07.012","article-title":"Microbial Imidazole Propionate Affects Responses to Metformin through p38\u03b3-Dependent Inhibitory AMPK Phosphorylation","volume":"32","author":"Koh","year":"2020","journal-title":"Cell Metab."},{"key":"10.1016\/j.isci.2025.113892_bib11","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2024.155416","article-title":"Preparation and characterisation of baicalin magnesium and its protective effect in ulcerative colitis via gut microbiota-bile acid axis modulation","volume":"126","author":"Zhang","year":"2024","journal-title":"Phytomedicine"},{"key":"10.1016\/j.isci.2025.113892_bib12","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2024.118355","article-title":"Baicalin suppresses macrophage JNK-mediated adipose tissue inflammation to mitigate insulin resistance in obesity","volume":"332","author":"Zhu","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.isci.2025.113892_bib13","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.ejmech.2017.03.004","article-title":"Therapeutic potentials of baicalin and its aglycone, baicalein against inflammatory disorders","volume":"131","author":"Dinda","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.isci.2025.113892_bib14","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2023.107032","article-title":"Baicalin and baicalein in modulating tumor microenvironment for cancer treatment: a comprehensive review with future perspectives","volume":"199","author":"Wang","year":"2024","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.isci.2025.113892_bib15","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejphar.2019.172457","article-title":"Baicalin improves intestinal microecology and abnormal metabolism induced by high-fat diet","volume":"857","author":"Ju","year":"2019","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.isci.2025.113892_bib16","doi-asserted-by":"crossref","first-page":"12621","DOI":"10.1039\/D1FO02407H","article-title":"Baicalin inhibits APEC-induced lung injury by regulating gut microbiota and SCFA production","volume":"12","author":"Peng","year":"2021","journal-title":"Food Funct."},{"key":"10.1016\/j.isci.2025.113892_bib17","article-title":"Microbial succinate promotes the response to metformin by upregulating secretory immunoglobulin a in intestinal immunity","volume":"17","author":"Zhang","year":"2025","journal-title":"Gut Microbes"},{"key":"10.1016\/j.isci.2025.113892_bib18","doi-asserted-by":"crossref","DOI":"10.1016\/j.scitotenv.2022.155937","article-title":"Polystyrene microplastic exposure induces insulin resistance in mice via dysbacteriosis and pro-inflammation","volume":"838","author":"Huang","year":"2022","journal-title":"Sci. Total Environ."},{"key":"10.1016\/j.isci.2025.113892_bib19","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/j.cell.2018.09.055","article-title":"Microbially Produced Imidazole Propionate Impairs Insulin Signaling through mTORC1","volume":"175","author":"Koh","year":"2018","journal-title":"Cell"},{"key":"10.1016\/j.isci.2025.113892_bib21","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s11892-018-1101-6","article-title":"Pathogenesis of Lipid Disorders in Insulin Resistance: a Brief Review","volume":"18","author":"Bjornstad","year":"2018","journal-title":"Curr. Diab. Rep."},{"key":"10.1016\/j.isci.2025.113892_bib22","doi-asserted-by":"crossref","DOI":"10.3390\/nu15051159","article-title":"Inflammation and Nutrition: Friend or Foe?","volume":"15","author":"Stumpf","year":"2023","journal-title":"Nutrients"},{"key":"10.1016\/j.isci.2025.113892_bib23","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1172\/JCI29069","article-title":"Inflammation and insulin resistance","volume":"116","author":"Shoelson","year":"2006","journal-title":"J. Clin. Investig."},{"key":"10.1016\/j.isci.2025.113892_bib24","doi-asserted-by":"crossref","DOI":"10.1038\/emm.2016.16","article-title":"AMPK activators: mechanisms of action and physiological activities","volume":"48","author":"Kim","year":"2016","journal-title":"Exp. Mol. Med."},{"key":"10.1016\/j.isci.2025.113892_bib25","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1016\/j.cmet.2014.09.018","article-title":"Metformin: from mechanisms of action to therapies","volume":"20","author":"Foretz","year":"2014","journal-title":"Cell Metab."},{"key":"10.1016\/j.isci.2025.113892_bib26","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1038\/s41574-019-0242-2","article-title":"Understanding the glucoregulatory mechanisms of metformin in type 2 diabetes mellitus","volume":"15","author":"Foretz","year":"2019","journal-title":"Nat. Rev. Endocrinol."},{"key":"10.1016\/j.isci.2025.113892_bib27","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1042\/bst0301064","article-title":"Regulation of fatty acid synthesis and oxidation by the AMP-activated protein kinase","volume":"30","author":"Hardie","year":"2002","journal-title":"Biochem. Soc. Trans."},{"key":"10.1016\/j.isci.2025.113892_bib28","doi-asserted-by":"crossref","DOI":"10.3390\/nu13061740","article-title":"High Fat Activates O-GlcNAcylation and Affects AMPK\/ACC Pathway to Regulate Lipid Metabolism","volume":"13","author":"Pang","year":"2021","journal-title":"Nutrients"},{"key":"10.1016\/j.isci.2025.113892_bib29","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1017\/S1461145711000976","article-title":"The effect of clozapine on the AMPK-ACC-CPT1 pathway in the rat frontal cortex","volume":"15","author":"Kim","year":"2012","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"10.1016\/j.isci.2025.113892_bib30","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1136\/gutjnl-2019-320204","article-title":"Interaction between drugs and the gut microbiome","volume":"69","author":"Weersma","year":"2020","journal-title":"Gut"},{"key":"10.1016\/j.isci.2025.113892_bib31","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/s41577-024-01014-8","article-title":"Short-chain fatty acids: linking diet, the microbiome and immunity","volume":"24","author":"Mann","year":"2024","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.isci.2025.113892_bib32","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1038\/nm.1870","article-title":"Inhibition of lipoprotein-associated phospholipase A2 reduces complex coronary atherosclerotic plaque development","volume":"14","author":"Wilensky","year":"2008","journal-title":"Nat. Med."},{"key":"10.1016\/j.isci.2025.113892_bib33","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1001\/jama.2014.11061","article-title":"Effect of darapladib on major coronary events after an acute coronary syndrome: the SOLID-TIMI 52 randomized clinical trial","volume":"312","author":"O'Donoghue","year":"2014","journal-title":"JAMA"},{"key":"10.1016\/j.isci.2025.113892_bib34","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1007\/s00125-017-4343-y","article-title":"60 years of metformin use: a glance at the past and a look to the future","volume":"60","author":"Marshall","year":"2017","journal-title":"Diabetologia"},{"key":"10.1016\/j.isci.2025.113892_bib35","doi-asserted-by":"crossref","DOI":"10.1016\/j.isci.2023.108082","article-title":"Metformin inhibits inflammatory response and endoplasmic reticulum stress to improve hypothalamic aging in obese mice","volume":"26","author":"Yang","year":"2023","journal-title":"iScience"},{"key":"10.1016\/j.isci.2025.113892_bib36","doi-asserted-by":"crossref","DOI":"10.1016\/j.isci.2023.106057","article-title":"Oral metformin transiently lowers post-prandial glucose response by reducing the apical expression of sodium-glucose co-transporter 1 in enterocytes","volume":"26","author":"Zubiaga","year":"2023","journal-title":"iScience"},{"key":"10.1016\/j.isci.2025.113892_bib38","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1186\/s12974-021-02330-9","article-title":"A new experimental design to study inflammation-related versus non-inflammation-related depression in mice","volume":"18","author":"Cardinal","year":"2021","journal-title":"Neuroinflammation"},{"key":"10.1016\/j.isci.2025.113892_bib39","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1111\/dom.15539","article-title":"The GPR40 novel agonist SZZ15-11 improves non-alcoholic fatty liver disease by activating the AMPK pathway and restores metabolic homeostasis in diet-induced obese mice","volume":"26","author":"Lei","year":"2024","journal-title":"Diabetes Obes. Metab."},{"key":"10.1016\/j.isci.2025.113892_bib40","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s40104-021-00581-3","article-title":"Short-chain fatty acids can improve lipid and glucose metabolism independently of the pig gut microbiota","volume":"12","author":"Zhou","year":"2021","journal-title":"J. Anim. Sci. Biotechnol."},{"key":"10.1016\/j.isci.2025.113892_bib41","doi-asserted-by":"crossref","DOI":"10.1016\/j.psj.2022.101742","article-title":"Dietary fibers with different viscosity regulate lipid metabolism via ampk pathway: roles of gut microbiota and short-chain fatty acid","volume":"101","author":"Li","year":"2022","journal-title":"Poult. Sci."},{"key":"10.1016\/j.isci.2025.113892_bib42","doi-asserted-by":"crossref","DOI":"10.3390\/ijms23031105","article-title":"Gut Microbiota and Short Chain Fatty Acids: Implications in Glucose Homeostasis","volume":"23","author":"Portincasa","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.isci.2025.113892_bib43","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1126\/science.aao5774","article-title":"Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes","volume":"359","author":"Zhao","year":"2018","journal-title":"Science (New York, NY)"},{"key":"10.1016\/j.isci.2025.113892_bib44","doi-asserted-by":"crossref","DOI":"10.1080\/19490976.2025.2467193","article-title":"Roseburia hominis improves host metabolism in diet-induced obesity","volume":"17","author":"Huang","year":"2025","journal-title":"Gut Microbes"},{"key":"10.1016\/j.isci.2025.113892_bib45","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/1758-5996-5-6","article-title":"Metformin: an old but still the best treatment for type 2 diabetes","volume":"5","author":"Rojas","year":"2013","journal-title":"Diabetol. Metab. Syndr."},{"key":"10.1016\/j.isci.2025.113892_bib46","doi-asserted-by":"crossref","first-page":"2421","DOI":"10.2147\/DDDT.S141675","article-title":"Metformin: a review of its potential indications","volume":"11","author":"Wang","year":"2017","journal-title":"Drug Des. Devel. Ther."},{"key":"10.1016\/j.isci.2025.113892_bib47","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s00228-014-1774-y","article-title":"A pharmacogenetic association between a variation in calpain 10 (CAPN10) gene and the response to metformin treatment in patients with type 2 diabetes","volume":"71","author":"Tk\u00e1\u010d","year":"2015","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"10.1016\/j.isci.2025.113892_bib48","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.2337\/db08-0896","article-title":"Reduced-function SLC22A1 polymorphisms encoding organic cation transporter 1 and glycemic response to metformin: a GoDARTS study","volume":"58","author":"Zhou","year":"2009","journal-title":"Diabetes"},{"key":"10.1016\/j.isci.2025.113892_bib49","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1136\/annrheumdis-2020-218329","article-title":"Activation of acid-sensing ion channel 3 by lysophosphatidylcholine 16:0 mediates psychological stress-induced fibromyalgia-like pain","volume":"79","author":"Hung","year":"2020","journal-title":"Ann. Rheum. Dis."},{"key":"10.1016\/j.isci.2025.113892_bib50","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2023.107033","article-title":"Baicalin circumvents anti-PD-1 resistance by regulating the gut microbiota metabolite short-chain fatty acids","volume":"199","author":"Yu","year":"2024","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.isci.2025.113892_bib51","first-page":"817","article-title":"A Microbiota-Derived Bacteriocin Targets the Host to Confer Diarrhea Resistance in Early-Weaned Piglets","volume":"24","author":"Hu","year":"2018","journal-title":"Microbe"},{"key":"10.1016\/j.isci.2025.113892_bib52","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/s41467-023-44373-x","article-title":"Gut microbiota facilitate chronic spontaneous urticaria","volume":"15","author":"Zhu","year":"2024","journal-title":"Nat. Commun."},{"key":"10.1016\/j.isci.2025.113892_bib53","doi-asserted-by":"crossref","first-page":"3439","DOI":"10.1111\/dom.15689","article-title":"Integrated biomarker profiling for predicting the response of type 2 diabetes to metformin","volume":"26","author":"Long","year":"2024","journal-title":"Diabetes Obes. Metab."},{"key":"10.1016\/j.isci.2025.113892_bib54","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.1038\/s41401-021-00703-7","article-title":"Lp-PLA2 inhibition prevents Ang II-induced cardiac inflammation and fibrosis by blocking macrophage NLRP3 inflammasome activation","volume":"42","author":"Lv","year":"2021","journal-title":"Acta Pharmacol. Sin."}],"container-title":["iScience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589004225021534?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589004225021534?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:46:36Z","timestamp":1782866796000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2589004225021534"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11]]},"references-count":52,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["S2589004225021534"],"URL":"https:\/\/doi.org\/10.1016\/j.isci.2025.113892","relation":{},"ISSN":["2589-0042"],"issn-type":[{"value":"2589-0042","type":"print"}],"subject":[],"published":{"date-parts":[[2025,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Roseburia hominis enriched by baicalin reverses the non-response to metformin via upregulating linolenic acid metabolism","name":"articletitle","label":"Article Title"},{"value":"iScience","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.isci.2025.113892","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"113892"}}