title: Comprehensive evaluation of the bactericidal activities of free bile acids in the large intestine of humans and rodents.
abstract: In addition to functioning as detergents that aid digestion of dietary lipids in the intestine, some bile acids have been shown to exhibit antimicrobial activity. However, detailed information on the bactericidal activities of the diverse molecular species of bile acid in humans and rodents is largely unknown. Here, we investigated the toxicity of 14 typical human and rodent free bile acids (FBAs) by monitoring intracellular pH, membrane integrity, and viability of a human intestinal bacterium,Bifidobacterium breveJapan Collection of Microorganisms (JCM) 1192T, upon exposure to these FBAs. Of all FBAs evaluated, deoxycholic acid (DCA) and chenodeoxycholic acid displayed the highest toxicities. Nine FBAs common to humans and rodents demonstrated that α-hydroxy-type bile acids are more toxic than their oxo-derivatives and β-hydroxy-type epimers. In five rodent-specific FBAs, β-muricholic acid and hyodeoxycholic acid showed comparable toxicities at a level close to DCA. Similar trends were observed for the membrane-damaging effects and bactericidal activities toBlautia coccoidesJCM 1395TandBacteroides thetaiotaomicronDSM 2079T, commonly represented in the human and rodent gut microbiota. These findings will help us to determine the fundamental properties of FBAs and better understand the role of FBAs in the regulation of gut microbiota composition.
authors.affiliation: Laboratory of Microbial Physiology, Research Faculty of Agriculture, Hokkaido University, Sapporo, Hokkaido 060-8589, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Laboratory of Microbial Physiology, Research Faculty of Agriculture, Hokkaido University, Sapporo, Hokkaido 060-8589, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Fukiya
authors.affiliation: Laboratory of Microbial Physiology, Research Faculty of Agriculture, Hokkaido University, Sapporo, Hokkaido 060-8589, Japan yokota@chem.agr.hokudai.ac.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yokota
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001438:Bacteroidaceae / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D000069984:Bifidobacterium breve / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D001647:Bile Acids and Salts / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D007420:Intestine, Large / Q000378:metabolism*; D042541:Intracellular Space / Q000187:drug effects; D051379:Mice; D050296:Microbial Viability / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D001647:Bile Acids and Salts
keywords: bile acids and salts; bile acids and salts/metabolism; bile acids and salts/physical chemistry; deoxycholic acid; gut microbiota; hyodeoxycholic acid; obesity; β-muricholic acid