Synbiotic microcapsules delivering Lactiplantibacillus Plantarum AR113 protect against acute pancreatitis via acetate-mediated modulation of the gut-pancreas axis

Acute pancreatitis (AP) urgently requires new therapeutic strategies. Here, we developed a maltose-alginate synbiotic microcapsule (AM-AR113) for intestinal delivery of Lactiplantibacillus plantarum AR113 and evaluated its protective effect in AP. AM-AR113 improved bacterial survival during storage and simulated gastrointestinal transit. In AP mice, AM-AR113 reduced pancreatic and ileal injury and decreased serum IL-6, TNF-α, and IL-1β. It also improved gut microbiota dysbiosis and markedly increased fecal acetate. Using an acetate kinase-deficient mutant (AR113Δ0187), we found that reduced acetate production was accompanied by weakened protection, whereas exogenous acetate reproduced the major protective effects. Acetate restored intestinal barrier-related markers, reduced serum DAO, LPS, and FITC-dextran levels, and was associated with reduced pancreatic MCP-1, decreased M1-associated inflammatory markers, increased Cd206 expression, and reduced Hdac3 expression. These findings suggest that AM-AR113 protects against AP at least partly through acetate-associated gut-pancreas axis regulation.