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Mounting evidence suggests that the gut microbiota modulates GLP\u20101 secretion via microbial metabolites, including short\u2010chain fatty acids and bile acid derivatives, while GLP\u20101 agonists reciprocally reshape microbial composition, influencing metabolic outcomes beyond their classical incretin functions. This bidirectional interplay has profound implications for precision medicine, as gut microbial signatures have been associated with variability in therapeutic response, raising the possibility that microbiome features could contribute to response stratification in future studies. Advances in pharmacomicrobiomics, multiomics integration and computational modelling now enable a more refined dissection of these interactions, illuminating potential microbial targets for intervention. Study discrepancies may arise from variations in host diet, baseline microbiome composition and genetic factors influencing GLP\u20101 signalling. Future studies should incorporate stratified analyses accounting for these confounders to understand causative mechanisms. This review collates current evidence on the microbiome\u2010mediated modulation of GLP\u20101 dynamics, evaluates the pharmacomicrobiomic impact of GLP\u20101 agonists and outlines future research directions at the interface of gut microbiota and incretin biology. By unravelling the complexities of this host\u2013microbe\u2013drug axis, the field moves closer to a paradigm of personalized metabolic medicine, where future GLP\u20101 therapeutic strategies may consider host metabolic and microbial context, optimizing efficacy and minimizing variability in patient response.<\/jats:p>","DOI":"10.1002\/bcp.70487","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T05:56:31Z","timestamp":1771394191000},"page":"1309-1325","source":"Crossref","is-referenced-by-count":31,"title":["GLP\u20101 agonists and the gut microbiome: A bidirectional relationship"],"prefix":"10.1002","volume":"92","author":[{"given":"Srinivas","family":"Kamath","sequence":"first","affiliation":[{"name":"School of Pharmacy and Biomedical Science Adelaide University  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole S. 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