Gut 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 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 . In a high-fat diet (HFD)-fed mice model, administration of live 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 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 and identify BSH as a potential target for preventing excessive fat deposition in humans and animals.