Abstract

Type 1 Diabetes Mellitus (T1DM) is a chronic autoimmune disease characterized by the destruction of pancreatic β-cells. Growing evidence indicates that immune dysregulation along the gut–lung axis contributes to its pathogenesis. This study aimed to develop a selenium-loaded sustained-release Schizophyllan (Se/s-SPG) composite and investigate its mechanism of action in alleviating T1DM-associated inflammatory immune responses through modulation of the gut microbiota and the Toll-like receptor 4 (TLR4)/Nuclear Factor kappa B (NF-κB) signaling pathway. A T1DM model was established using non-obese diabetic (NOD)/LtJ mice. Comprehensive analyses were performed, including 16 S rRNA sequencing, RNA sequencing (RNA-seq), Western blot (WB), Enzyme-linked immunosorbent assay (ELISA), and Flow Cytometry to assess the effects of Se/s-SPG on gut microbial diversity, pancreatic structure and function, immune cell subset distribution, and inflammatory signaling pathways. The results demonstrated that Se/s-SPG significantly improved glucose metabolism, restored intestinal and pulmonary barrier integrity, and regulated T cell subset differentiation as well as macrophage polarization. This study proposes a novel intervention strategy targeting the gut–lung axis for T1DM and highlights its potential for clinical translation. Graphical abstract The alternative text for this image may have been generated using AI.