Bifidobacterium Pseudolongum-Derived Acetate Attenuates Acute Pancreatitis Through GPR43-Mediated Suppression of M1 Macrophage Polarization.

Acute pancreatitis (AP) is characterized by gut microbiota dysbiosis, which is marked by an expansion of pathogenic bacteria and a pronounced depletion of beneficial taxa, including Bifidobacterium. While Bifidobacterium pseudolongum (B. pseudolongum) possesses known probiotic properties, its potential role in protecting against AP has yet to be determined. This study shows that B. pseudolongum alleviates pancreatic damage, inflammation, and apoptosis in mice with caerulein-induced and pancreatic duct ligation-induced AP by enhancing gut barrier function and microbiota diversity. Metabolomics identifies acetate as its key metabolite, and the ackA gene is essential for acetate biosynthesis. Acetate supplementation protects against AP. Mechanistically, acetate acts via GPR43 to inhibit macrophage M1 polarization, and macrophage depletion abrogates this protection. Clinically, the fecal B. pseudolongum abundance is reduced in AP patients and is correlated with disease severity. These findings reveal a microbiota-metabolite-immune axis in AP and highlight the potential of B. pseudolongum and acetate supplementation as novel therapeutic strategies for AP.