Effect of various antibiotics on modulation of intestinal microbiota and bile acid profile in mice

Toxicol Appl Pharmacol. 2014 Jun 1;277(2):138-45. doi: 10.1016/j.taap.2014.03.009. Epub 2014 Mar 20.

Abstract

Antibiotic treatments have been used to modulate intestinal bacteria and investigate the role of intestinal bacteria on bile acid (BA) homeostasis. However, knowledge on which intestinal bacteria and bile acids are modified by antibiotics is limited. In the present study, mice were administered various antibiotics, 47 of the most abundant bacterial species in intestine, as well as individual BAs in plasma, liver, and intestine were quantified. Compared to the two antibiotic combinations (vancomycin+imipenem and cephalothin+neomycin), the three single antibiotics (metronidazole, ciprofloxacin and aztreonam) have less effect on intestinal bacterial profiles, and thus on host BA profiles and mRNA expression of genes that are important for BA homeostasis. The two antibiotic combinations decreased the ratio of Firmicutes to Bacteroidetes in intestine, as well as most secondary BAs in serum, liver and intestine. Additionally, the two antibiotic combinations significantly increased mRNA of the hepatic BA uptake transporters (Ntcp and Oatp1b2) and canalicular BA efflux transporters (Bsep and Mrp2), but decreased mRNA of the hepatic BA synthetic enzyme Cyp8b1, suggesting an elevated enterohepatic circulation of BAs. Interestingly, the two antibiotic combinations tended to have opposite effect on the mRNAs of most intestinal genes, which tended to be inhibited by vancomycin+imipenem but stimulated by cephalothin+neomycin. To conclude, the present study clearly shows that various antibiotics have distinct effects on modulating intestinal bacteria and host BA metabolism.

Keywords: Antibiotics; Bile acids; Enterohepatic circulation; Intestinal bacteria; Intestine; Liver.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 11
  • ATP-Binding Cassette Transporters / drug effects
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism
  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Bacteria / classification
  • Bacteria / drug effects*
  • Bacteria / growth & development
  • Bile Acids and Salts / blood
  • Bile Acids and Salts / metabolism*
  • Drug Therapy, Combination
  • Enterohepatic Circulation
  • Gene Expression Regulation
  • Intestinal Mucosa / metabolism
  • Intestines / drug effects*
  • Intestines / microbiology
  • Liver / drug effects
  • Liver / metabolism
  • Liver-Specific Organic Anion Transporter 1
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Multidrug Resistance-Associated Proteins / drug effects
  • Multidrug Resistance-Associated Proteins / genetics
  • Multidrug Resistance-Associated Proteins / metabolism
  • Organic Anion Transporters, Sodium-Dependent / drug effects
  • Organic Anion Transporters, Sodium-Dependent / genetics
  • Organic Anion Transporters, Sodium-Dependent / metabolism
  • Organic Anion Transporters, Sodium-Independent / drug effects
  • Organic Anion Transporters, Sodium-Independent / genetics
  • Organic Anion Transporters, Sodium-Independent / metabolism
  • RNA, Messenger / metabolism
  • Steroid 12-alpha-Hydroxylase / genetics
  • Steroid 12-alpha-Hydroxylase / metabolism
  • Symporters / drug effects
  • Symporters / genetics
  • Symporters / metabolism

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 11
  • ATP-Binding Cassette Transporters
  • Abcb11 protein, mouse
  • Anti-Bacterial Agents
  • Bile Acids and Salts
  • Liver-Specific Organic Anion Transporter 1
  • Multidrug Resistance-Associated Proteins
  • Organic Anion Transporters, Sodium-Dependent
  • Organic Anion Transporters, Sodium-Independent
  • RNA, Messenger
  • Slco1b2 protein, mouse
  • Symporters
  • sodium-bile acid cotransporter
  • multidrug resistance-associated protein 2
  • Steroid 12-alpha-Hydroxylase