Analysis of metabolome changes in the bile acid pool in feces and plasma of antibiotic-treated rats

Toxicol Appl Pharmacol. 2019 Jan 15:363:79-87. doi: 10.1016/j.taap.2018.11.012. Epub 2018 Nov 28.

Abstract

The bile acid-liver-gut microbiota axis plays an important role in the host's health. The gut microbiota has an impact on the bile acid pool, but also the bile acids themselves can influence the gut microbiota composition. In this study, six antibiotics from five different classes (i.e. lincosamides, glycopeptides, macrolides, fluoroquinolones, aminoglycosides) were used to modulate microbial communities of Wistar rats to elucidate changes in the bile acid metabolism and to identify key metabolites in the bile acid pool related to gut microbial changes. 20 primary and secondary bile acids were analyzed in plasma and feces of control and treated animals. Antibiotics treatment induced significant changes in primary and secondary bile acids in both matrices. Taurine-conjugated primary bile acids significantly increased in plasma and feces. Contrary, cholic acid and most of the analyzed secondary bile acids significantly decreased in plasma, and cholic acid accumulated in the feces after treatment with all antibiotics but roxithromycin. Despite the different activity spectra of the antibiotics applied against gut microbes, the overall effect on the bile acid pool tended to be similar in both matrices except for streptomycin. These results show that changes in the gut microbial community affect the bile acid pool in plasma and feces and that changes in the bile acid profile can be indicative of alterations of the gut microbiome. Due to the important role of bile acids for the host, changes in the bile acid pool can have severe consequences for the host.

Keywords: Antibiotics; Bile acid profiling; Gut microbiome; Metabolomics; Microbiome-related metabolites; Repeated dose oral toxicity study.

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / adverse effects*
  • Bile Acids and Salts / analysis
  • Bile Acids and Salts / metabolism*
  • Feces / chemistry
  • Female
  • Gastrointestinal Microbiome / drug effects*
  • Gastrointestinal Microbiome / physiology
  • Lipid Metabolism / drug effects
  • Male
  • Metabolome / drug effects*
  • Metabolomics
  • Models, Animal
  • Rats
  • Rats, Wistar

Substances

  • Anti-Bacterial Agents
  • Bile Acids and Salts