The effect of chenodeoxycholic acid inclusion in a plant-based diet on the crosstalk between gut microbiota and bile acids in tilapia

Chenodeoxycholic acid (CDCA), a key component of fish bile acids, has been widely confirmed to promote growth performance and increase the diversity of intestinal flora. This study systematically investigated the effects of dietary CDCA supplementation (75–300 mg/kg) on hepato-intestinal health and bile acid-microbiota interactions in tilapia ( Oreochromis niloticus ) fed plant-based diets. Results revealed that CDCA supplementation significantly reduced hepatic and whole-body lipid content. Furthermore, it decreased serum activities of aspartate transaminase (AST) and alanine transaminase (ALT), while increasing total bilirubin levels. Notably, 300 mg/kg CDCA supplementation significantly reduced serum glucose, triglycerides, low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), albumin, and total protein levels, indicating improved lipid metabolism and reduced hepatic steatosis. At the molecular level, 75 mg/kg and 150 mg/kg dietary CDCA supplementation downregulated the expression of bile acid metabolism related genes ( fxr ) and upregulated the expression of cyp7a1 . Furthermore, 150 mg/kg dietary CDCA supplementation increased intestinal villus length and muscle layer thickness, as well as increasing the abundance of beneficial bacteria such as Firmicutes, thereby improving the stability of the gut microbiota. Collectively, these results highlight the potential of a dietary supplementation of 150 mg/kg CDCA as a strategic intervention to mitigate the adverse effects of plant-based diets in aquaculture, offering a promising avenue for sustainable and healthy fish production. • Incorporating chenodeoxycholic acid (CDCA) into tilapia’s plant-based diets modulates gallbladder bile acid profiles and alters the composition of their gut microbiota. • CDCA enhances bile acid content by upregulating cyp7a1 through the inhibition of fxr expression, promoting hepatic lipid metabolism and reducing hepatocyte vacuolation. • CDCA boosts beneficial gut bacteria (e.g., Firmicutes, Akkermansia ), reduces fat accumulation, improves intestinal villus height and muscle layer thickness, enhancing tilapia’s overall health.