Trehalose ameliorates severe acute pancreatitis by modulating gut microbial metabolism

This study investigates the role of trehalose in modulating gut microbiota metabolism and alleviating symptoms of severe acute pancreatitis (SAP). Here, we found that gut microbial metabolism was imbalanced in SAP. In particular, we observed increased lipid metabolism and decreased carbohydrate and amino acid metabolism, which were reversed by gut microbiota depletion. Moreover, the production of trehalose was significantly increased after gut microbiota depletion. Interestingly, trehalose treatment effectively reduced pancreatic injury and ameliorated the SAP-induced microbial metabolism imbalance by promoting carbohydrate metabolism and suppressing lipid metabolism. The effect of trehalose was depend on the gut microbiota, especially the expansion of Muribaculaceae. Mechanistically, trehalose-remodelled gut microbiota suppressed SAP-induced increases in serum TG, IL-6, IL-17A, and TNF-α levels, inhibited caspase-3-mediated apoptosis, and reduced macrophage infiltration into the pancreas. Overall, our study revealed that trehalose ameliorates SAP by modulating gut microbial metabolism homeostasis, providing new insights into the "microbial metabolism‒gut‒pancreatic axis".