Extracellular vesicles from Akkermansia muciniphila protect streptozotocin-induced diabetic mice by regulating glucose homeostasis, oxidative stress, and immune tolerance.

INTRODUCTION: Accumulating evidence suggests that extracellular vesicles (EVs) derived from gut microbiota play important roles in modulating host metabolism and immune responses, thereby influencing the development of metabolic disorders including diabetes mellitus. Akkermansia muciniphila (A. muciniphila), a mucin-degrading bacterium, exerts beneficial effects on glucose metabolism and immune regulation.

METHODS: This study investigated the protective effects of A. muciniphila-derived extracellular vesicles (AmEVs) in streptozotocin (STZ)-induced type 1 diabetes mellitus (T1DM) mice. Metabolic parameters, pancreatic histology, oxidative stress, inflammatory cytokines, and regulatory T cell (Treg) responses were assessed. Anti-CD25-mediated Treg depletion was performed to evaluate the functional role of Tregs.

RESULTS AND DISCUSSION: STZ-induced T1DM mice exhibited a significantly reduced abundance of A. muciniphila. AmEV treatment ameliorated hyperglycemia and improved glucose tolerance, insulin tolerance, and pyruvate tolerance, showing greater metabolic improvement than heat-inactivated A. muciniphila. AmEVs preserved pancreatic islet morphology and enhanced β-cell function, accompanied by improved systemic metabolic parameters. In addition, AmEVs reduced oxidative stress and suppressed inflammatory cytokine production while enhancing Treg-associated immunoregulation in pancreatic tissue. Importantly, anti-CD25-mediated Treg depletion partially reversed the metabolic and anti-inflammatory benefits of AmEV treatment. These findings suggest that AmEVs alleviate diabetic pathology through coordinated metabolic and immune regulation. The protective effects are at least partly dependent on Treg-mediated immunoregulation, highlighting the potential of AmEVs as microbiota-derived therapeutic candidates for T1DM.