Inulin prebiotic ameliorates type 1 diabetes dictating regulatory T cell homing via CCR4 to pancreatic islets and butyrogenic gut microbiota in murine model.

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.