Agradecimentos: The authors are grateful to Elaine Medeiros Floriano and Wander Ribeiro (Ribeirão Preto Medical School, University of São Paulo), for their assistance in processing tissue for histopathological analysis. The authors thank Editage (www.editage.com) for English language editing. This research was funded by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) under agreement nos. 2018/14815-0 (Young Researcher Project) and 2019/13858-0 (Masters); Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Ver menos

Abstract: Gut dysbiosis is linked to Type 1 diabetes mellitus (T1D). Inulin, a prebiotic, modulates the gut microbiota, promoting beneficial bacteria that produce essential short-chain fatty acids for immune regulation. However, how inulin affects T1D remains uncertain. Using a streptozotocin-induced (STZ) mouse model, we studied inulin's protective effects. Remarkably, STZ+INU mice resisted T1D, with none developing the disease. They had lower blood glucose, reduced pancreatic inflammation, and normalized serum insulin compared to STZ+SD mice. STZ+INU mice also had enhanced mucus production, abundant Bifidobacterium, Clostridium cluster IV, Akkermansia muciniphila, and increased fecal butyrate. In cecal lymph nodes, we observed fewer CD4+Foxp3+ Tregs expressing CCR4 and more Foxp3+CCR4+ cells in pancreatic islets, with higher CCL17 expression. This phenotype was absent in CCR4-deficient mice on inulin. Inulin supplementation effectively protects against experimental T1D by recruiting CCR4+ Treg cells via CCL17 into the pancreas and altering the butyrate-producing microbiota Ver menos