16S rRNA gene amplicon analysis of pig gut microbiota (PRJCA032509)
Our results revealed that PDCoV infection causes microbiota dysbiosis in pigs, significantly reducing the intestinal abundance of Bacteroides fragilis, which correlated with disruptions in bile acid metabolism. Colonization with bile salt hydrolase (BSH)-producing B. fragilis increased the load of unconjugated bile acids and inhibited PDCoV infection, highlighting the role of microbiota-associated bile acid metabolism in viral pathogenesis. LCA, a prominent unconjugated bile acid, was shown to effectively inhibit PDCoV infection in porcine small intestinal epithelial cells and porcine intestinal enteroids. Notably, LCA inhibited PDCoV replication independently of bile acid receptor signaling and innate immune modulation. Mechanistic studies indicated that LCA prevents PDCoV infection by disrupting the viral entry process, specifically inhibiting binding between the PDCoV spike protein and its cellular receptor, aminopeptidase N. In vivo experiments further confirmed that LCA significantly inhibits PDCoV infection in piglets.