{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T01:34:11Z","timestamp":1793151251254,"version":"4.5.0"},"reference-count":140,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Interindividual variability in clinical response to glucagon-like peptide-1 receptor agonists (GLP-1 RAs) represents a significant challenge in the management of obesity and type 2 diabetes (T2D). In recent years, growing interest has focused on the potential role of the gut microbiota as a biological modifier of incretin-based therapy. This narrative review synthesizes current preclinical and human evidence on the bidirectional interactions between GLP-1 RAs and the intestinal microbial ecosystem, with particular attention to microbial composition, metabolite production (including short-chain fatty acids and bile acids), intestinal barrier integrity, and inflammatory signaling. Experimental models consistently demonstrate that GLP-1 RAs can remodel gut microbial communities and influence metabolite profiles. In human studies, GLP-1 RA therapy has been associated with changes in microbial diversity and enrichment of specific taxa; however, most available data remain observational and associative. Small exploratory cohorts suggest that baseline microbiota composition may correlate with differential metabolic response, giving rise to the responder\/non-responder framework. Nevertheless, definitions of response are heterogeneous, study populations are limited in size, and mechanistic causality has not been established. Importantly, microbiota changes observed during GLP-1 RA therapy may be influenced by confounding factors such as weight loss magnitude, dietary modifications, and concomitant treatments, particularly metformin. Functional pathway inferences frequently rely on 16S rRNA-based predictions rather than direct metabolomic measurements, warranting cautious interpretation. Overall, current evidence supports the hypothesis that host\u2013microbiome interactions may contribute to therapeutic heterogeneity, but robust longitudinal and interventional human studies are required before microbiome-informed stratification or adjunctive microbiota-targeted interventions can be considered for clinical implementation. Elucidating these interactions may ultimately refine precision approaches to incretin-based therapy in metabolic disease.<\/jats:p>","DOI":"10.3389\/fendo.2026.1858420","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T05:38:45Z","timestamp":1783316325000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["The gut microbiota as a potential determinant of response to GLP-1 receptor agonists: a narrative review"],"prefix":"10.3389","volume":"17","author":[{"given":"Luigi Regenburgh","family":"De La Motte","sequence":"first","affiliation":[{"name":"Unit\u00e0 Operativa Complessa UOC Laboratory of Clinical Medicine with Specialized Areas, Istituto di Ricovero e Cura a Carattere Scientifico IRCCS MultiMedica","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Carreras","sequence":"additional","affiliation":[{"name":"Unit\u00e0 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