Gut microbiota-derived deoxycholic acid promotes pancreatic regeneration following acute pancreatitis via Reg3a signaling pathway

Recovery from acute pancreatitis (AP) involves complex biological processes, and the mechanisms governing pancreatic repair remain unclear. In a clinical cohort during the recovery phase of AP, impaired pancreatic recovery was associated with intestinal dysbiosis, depletion of the microbial bile salt hydrolase gene (bsh), and reduced levels of the secondary bile acid deoxycholic acid (DCA). Consistently, in mouse models, depletion or reshaping of the gut microbiota markedly altered the course of pancreatic repair, whereas supplementation of mice with BSH-overexpressing strains or direct administration of DCA accelerated recovery. Mechanistic investigations further indicated that DCA activates the nuclear receptor pathway of PXR/RXR, subsequently enhancing transcription of the regeneration-associated gene Reg3α. Elevated Reg3α expression further upregulated Ptf1a, a critical factor maintaining acinar cell identity, thereby inhibiting aberrant ADM and facilitating recovery of damaged acinar cell function. Together, these findings identify a gut microbiota related signaling axis associated with pancreatic repair after AP.