Abstract

Hypertriglyceridemic acute pancreatitis (HTG-AP) is an increasingly important form of acute pancreatitis caused by markedly elevated serum triglyceride (TG) levels. A close relationship exists between the gut dysbiosis and HTG-AP; however, the mechanisms mediating this association have yet to be elucidated. Bifidobacterium , a widely used probiotic, has been extensively applied in food fermentation and dietary supplements. Here, we observed a significant depletion of Bifidobacterium breve ( B. breve ) in the HTG-AP mice. Administration of the probiotic strain B. breve MYQQ-7 significantly alleviated lipotoxicity and pancreatic injury in HTG-AP mice, which was accompanied by an increase in the expression of peroxisome proliferator-activated receptor gamma (PPARγ). Mechanistically, exopolysaccharides (EPS) of B. breve MYQQ-7 were identified as the key bioactive component mediating these protective effects. Treatment with EPS derived from B. breve MYQQ-7 activates the PPARγ signaling pathway, leading to the suppression of pancreatic lipase (PNLIP) expression, and attenuation of free fatty acid (FFA)-mediated lipotoxicity. Notably, co-administration of the PPARγ antagonist GW9662 abolished the protective effects of EPS, confirming the involvement of PPARγ signaling in EPS-mediated effects. Collectively, our findings indicate that B. breve is protective against HTG-AP and suggest the potential to develop therapeutic strategies for patients with HTG-AP.