Fasting and refeeding triggers specific changes in bile acid profiles and gut microbiota

Background: Bile acids (BAs) are closely related to nutrient supply and modified by gut microbiota. Gut microbiota perturbations shape BA composition, which further affects host metabolism.

Methods: We investigated BA profiles in plasma, feces, and liver of mice fed ad libitum, fasted for 24 h, fasted for 24 h and then refed for 24 h using ultraperformance liquid chromatography coupled to tandem mass spectrometry. Gut microbiota was measured by 16S rRNA gene sequencing. Expressions of BA biosynthesis-related genes in the liver and BA reabsorption-related genes in the ileum were analyzed.

Findings: Compared with the controls, unconjugated primary BAs (PBAs) and unconjugated secondary BAs (SBAs) in plasma were decreased whereas conjugated SBAs in plasma, unconjugated PBAs, unconjugated SBAs and conjugated SBAs in feces, and unconjugated SBAs in liver were increased in the fasting mice. The expression of BA biosynthesis-related genes in the liver and BA reabsorption-related genes in the ileum were decreased in the fasting mice compared with the controls. Compared with the controls, Akkermansia, Parabacteroides, Muribaculum, Eubacterium_coprostanoligenes and Muribaculaceae were increased in the fasting mice whereas Lactobacillus and Bifidobacterium were decreased. All these changes in BAs and gut microbiota were recovered under refeeding. Akkermansia was negatively correlated with plasma levels of unconjugated PBAs, unconjugated SBAs and glucose, whereas it was positively correlated with plasma conjugated SBAs, fecal unconjugated PBAs, and fecal unconjugated SBAs.

Conclusions: We characterized the BA profiles, gut microbiota, and gene expression responsible for BA biosynthesis and intestinal reabsorption to explore their rapid changes in response to food availability. Our study highlighted the rapid effect of nutrient supply on BAs and gut microbiota.