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

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.