Trehalose ameliorates severe acute pancreatitis by modulating the gut microbial metabolism

Severe Acute Pancreatitis (SAP) is an acute, severe, and high-mortality special type of pancreatitis, often accompanied by gut microbiota disorders. Gut microbiota and its derived metabolites are involved in SAP progression, but gut microbial metabolism in SAP and their roles remain unclear. In this study, we found that gut microbial metabolism homeostasis was imbalanced in SAP, especially the increase of lipids metabolism and decrease of carbohydrate & amino acid metabolism, which were reversed by depleting the gut microbiota. Trehalose in microbial carbohydrate metabolism significantly increased after depleting gut microbiota. Interestingly, oral trehalose effectively reduced pancreatic injury and ameliorated the SAP-induced microbial metabolism imbalance by increasing carbohydrate metabolism and decreasing lipids metabolism, especially increasing galactose metabolism. The role of trehalose was shown to be dependent on gut microbiota via FMT, especially the inhibition of Lactobacillaceae and the expansion of Muribaculaceae . Mechanistically, trehalose-remodeled gut microbiota reduced SAP-induced increases in serum TG, IL-6, IL-17A, and TNF-α, and inhibited caspase-3-mediated apoptosis and macrophage infiltration in the pancreas. Overall, our study revealed that trehalose ameliorates SAP by modulating the gut microbial metabolism homeostasis, which provides new insights into alterations of gut microbial metabolism and the “microbial metabolism-gut-pancreatic axis” to treat pancreatic diseases.