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 breve Japan 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 to Blautia coccoides JCM 1395T and Bacteroides thetaiotaomicron DSM 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.
Highlights
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
Our previous study showed that deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA) dissipated the pH of Japan Collection of Microorganisms (JCM) 1192T at concentrations 10-fold lower than the necessary concentration of cholic acid (CA), indicating 10-fold greater membrane-damaging activity for DCA and CDCA compared with CA [7]
To demonstrate the bactericidal activities of human and rodent free bile acid (FBA) toward bacteria belonging to the Firmicutes and Bacteroidetes phyla, we investigated the membrane integrity and viability of B. coccoides JCM 1395T and B. thetaiotaomicron DSM 2079T after exposure to rodent FBAs, as well as CA and DCA, at the viability loss-inducing concentrations determined for B. breve JCM 1192T
Summary
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. Similar trends were observed for the membrane-damaging effects and bactericidal activities to Blautia coccoides JCM 1395T and Bacteroides thetaiotaomicron DSM 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.—Watanabe, M., S. In addition to CA and CDCA, there are two primary bile acids that are not present in humans, namely, -muricholic acid (MCA) and -MCA These bile acids are transformed into rodent secondary bile acids by the indigenous intestinal microbes: -MCA from -MCA [3] and hyodeoxycholic acid (HDCA) from -MCA, -MCA, -MCA, and -MCA [4]. We discovered using CA-feeding experiments that bile acids are host factors that regulate the cecal
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