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

Introduction: ), a mucin-degrading bacterium, exerts beneficial effects on glucose metabolism and immune regulation. Methods: -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: . 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.