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

Abstract

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 Yi Zhang, Hongyan Qi and Long Wang contributed equally to this work.

The Beneficial Effects of Dietary Interventions on Gut Microbiota—An Up-to-Date Critical Review and Future Perspectives

“…Akkermansia was negatively correlated with plasma unconjugated primary and secondary bile acids and glucose levels but positively correlated with plasma conjugated secondary bile acids and faecal unconjugated forms of both bile acids. In contrast, Lactobacillus and Bifidobacterium were positively correlated with plasma levels of unconjugated primary bile acids and unconjugated secondary bile acids [57]. These results are supported by other authors who demonstrated the involvement of Lactobacillus and Bifidobacterium in bile acid metabolism, including deconjugation, via bile salt hydrolases or 7α-dehydroxylation [74].…”

“…The results obtained for the Akkermansia population are also heterogeneous. IF resulted in increased Akkermansia abundance in five studies, mainly comprising short-term IF [57,65,67,69,72], but at lower levels during long-term IF [65]. Similar inconsistencies are observed in studies that reported variations of other genera, such as Clostridium or Allobaculum [58,66].…”

“…The Lactobacillus genus, which is considered highly relevant for the microbiome composition and is generally linked to improved health status, was increased by TRF in five reports [63,65,[68][69][70], while in the other three, it was lowered [57,64,71]. The results obtained for the Akkermansia population are also heterogeneous.…”