Gut Bifidobacterium pseudocatenulatum protects against fat deposition by enhancing secondary bile acid biosynthesis

Gut microbiome is crucial for lipid metabolism in humans and animals. However, how specific gut microbiota and their associated metabolites impact fat deposition remains unclear. In this study, we demonstrated that the colonic microbiome of lean and obese pigs differentially contributes to fat deposition, as evidenced by colonic microbiota transplantation experiments. Notably, the higher abundance of Bifidobacterium pseudocatenulatum was significantly associated with lower backfat thickness in lean pigs. Microbial-derived lithocholic acid (LCA) species were also significantly enriched in lean pigs and positively correlated with the abundance of B. pseudocatenulatum . In a high-fat diet (HFD)-fed mice model, administration of live B. pseudocatenulatum decreased fat deposition and enhances colonic secondary bile acid biosynthesis. Importantly, pharmacological inhibition of the bile salt hydrolase (BSH), which mediates secondary bile acid biosynthesis, impaired the anti-fat deposition effect of B. pseudocatenulatum in antibiotic-pretreated, HFD-fed mice. Furthermore, dietary LCA also decreased fat deposition in HFD-fed rats and obese pig models. These findings provide mechanistic insights into the anti-fat deposition role of B. pseudocatenulatum and identify BSH as a potential target for preventing excessive fat deposition in humans and animals. Graphical This figure highlights how gut microbiota and bile acids regulate fat deposition in lean and obese pigs. Lean pigs showed increased microbial-derived lithocholic acid (LCA) species and muricholic acid species, closely linked to the abundance of Bifidobacterium pseudocatenulatum . In contrast, obese pigs exhibited gut microbiota favoring hyodeoxycholic acid species accumulation. In high-fat diet-fed mice, live B. pseudocatenulatum supplementation enhances secondary bile acid synthesis, especially LCA production, and reduces fat mass, while bile salt hydrolase (BSH) inhibition negates these effects. Dietary LCA similarly lowers fat deposition in obese pigs and rats. These findings provide mechanistic insights into the anti-fat deposition role of B. pseudocatenulatum and identify BSH as a potential target for preventing excessive fat deposition in humans and animals. Highlights The gut microbiota composition and function differ significantly between lean and obese pigs, and breed-specific microbiomes regulate fat deposition. Gut Bifidobacterium pseudocatenulatum protects against fat deposition by enhancing secondary bile acid biosynthesis. Dietary supplementation with lithocholic acid also helps prevent fat deposition.