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The multifactorial nature of T1D involves both genetic and environmental components, with recent research focusing on the gut microbiome as a crucial environmental factor in T1D pathogenesis. The gut microbiome and its metabolites play an important role in modulating immunity and autoimmunity. In recent years, studies have revealed significant alterations in the taxonomic and functional composition of the gut microbiome associated with the development of islet autoimmunity and T1D. These changes include reduced production of short-chain fatty acids, altered bile acid and tryptophan metabolism, and increased intestinal permeability with consequent perturbations of host (auto)immune responses. Methods\/Results: In this review, we summarize and discuss recent observational, mechanistic and etiological studies investigating the gut microbiome in T1D and elucidating the intricate role of gut microbes in T1D pathogenesis. Moreover, we highlight the recent advances in intervention studies targeting the microbiota for the prevention or treatment of human T1D. Conclusions: A deeper understanding of the evolution of the gut microbiome before and after T1D onset and of the microbial signals conditioning host immunity may provide us with essential insights for exploiting the microbiome as a prognostic and therapeutic tool.<\/jats:p>","DOI":"10.3390\/metabo15020138","type":"journal-article","created":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T05:34:26Z","timestamp":1739943266000},"page":"138","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["From Microbes to Metabolites: Advances in Gut Microbiome Research in Type 1 Diabetes"],"prefix":"10.3390","volume":"15","author":[{"given":"Lente","family":"Blok","sequence":"first","affiliation":[{"name":"Department of Internal and Vascular Medicine, Amsterdam University Medical Center, Location AMC, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nordin","family":"Hanssen","sequence":"additional","affiliation":[{"name":"Department of Internal and Vascular Medicine, Amsterdam University Medical Center, Location AMC, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Nieuwdorp","sequence":"additional","affiliation":[{"name":"Department of Internal and Vascular Medicine, Amsterdam University Medical Center, Location AMC, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7742-0092","authenticated-orcid":false,"given":"Elena","family":"Rampanelli","sequence":"additional","affiliation":[{"name":"Department of Internal and Vascular Medicine, Amsterdam University Medical Center, Location AMC, 1105 AZ Amsterdam, The Netherlands"},{"name":"Amsterdam Institute for Infection and Immunity (AII), Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/S2213-8587(22)00218-2","article-title":"Global incidence, prevalence, and mortality of type 1 diabetes in 2021 with projection to 2040: A modelling study","volume":"10","author":"Gregory","year":"2022","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Burrack, A.L., Martinov, T., and Fife, B.T. 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