Dataset Information

Bile Acid 7?-Dehydroxylating Gut Bacteria Secrete Antibiotics that Inhibit Clostridium difficile: Role of Secondary Bile Acids.

ABSTRACT: Clostridium scindens biotransforms primary bile acids into secondary bile acids, and is correlated with inhibition of Clostridium difficile growth in vivo. The aim of the current study was to determine how C. scindens regulates C. difficile growth in vitro and if these interactions might relate to the regulation of gut microbiome structure in vivo. The bile acid 7?-dehydroxylating gut bacteria, C. scindens and C. sordellii, were found to secrete the tryptophan-derived antibiotics, 1-acetyl-?-carboline and turbomycin A, respectively. Both antibiotics inhibited growth of C. difficile and other gut bacteria. The secondary bile acids, deoxycholic acid and lithocholic acid, but not cholic acid, enhanced the inhibitory activity of these antibiotics. These antibiotics appear to inhibit cell division of C. difficile. The results help explain how endogenously synthesized antibiotics and secondary bile acids may regulate C. difficile growth and the structure of the gut microbiome in health and disease.

SUBMITTER: Kang JD

PROVIDER: S-EPMC6338514 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Bile Acid 7α-Dehydroxylating Gut Bacteria Secrete Antibiotics that Inhibit Clostridium difficile: Role of Secondary Bile Acids.

Kang Jason D JD Myers Christopher J CJ Harris Spencer C SC Kakiyama Genta G Lee In-Kyoung IK Yun Bong-Sik BS Matsuzaki Keiichi K Furukawa Megumi M Min Hae-Ki HK Bajaj Jasmohan S JS Zhou Huiping H Hylemon Phillip B PB

Cell chemical biology 20181025 1

Clostridium scindens biotransforms primary bile acids into secondary bile acids, and is correlated with inhibition of Clostridium difficile growth in vivo. The aim of the current study was to determine how C. scindens regulates C. difficile growth in vitro and if these interactions might relate to the regulation of gut microbiome structure in vivo. The bile acid 7α-dehydroxylating gut bacteria, C. scindens and C. sordellii, were found to secrete the tryptophan-derived antibiotics, 1-acetyl-β-car ...[more]

PMID: 30482679

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Project description:Bile acids are important cholesterol-derived nutrient signaling hormones, synthesized in the liver, that act as detergents to solubilize dietary lipids. Bile acid 7?-dehydroxylating gut bacteria generate the toxic bile acids deoxycholic acid and lithocholic acid from host bile acids. The ability of these bacteria to remove the 7-hydroxyl group is partially dependent on 7?-hydroxysteroid dehydrogenase (HSDH) activity, which reduces 7-oxo-bile acids generated by other gut bacteria. 3?-HSDH has an important enzymatic activity in the bile acid 7?-dehydroxylation pathway. 12?-HSDH activity has been reported for the low-activity bile acid 7?-dehydroxylating bacterium Clostridium leptum; however, this activity has not been reported for high-activity bile acid 7?-dehydroxylating bacteria, such as Clostridium scindens, Clostridium hylemonae, and Clostridium hiranonis Here, we demonstrate that these strains express bile acid 12?-HSDH. The recombinant enzymes were characterized from each species and shown to preferentially reduce 12-oxolithocholic acid to deoxycholic acid, with low activity against 12-oxochenodeoxycholic acid and reduced activity when bile acids were conjugated to taurine or glycine. Phylogenetic analysis suggests that 12?-HSDH is widespread among Firmicutes, Actinobacteria in the Coriobacteriaceae family, and human gut ArchaeaIMPORTANCE 12?-HSDH activity has been established in the medically important bile acid 7?-dehydroxylating bacteria C. scindens, C. hiranonis, and C. hylemonae Experiments with recombinant 12?-HSDHs from these strains are consistent with culture-based experiments that show a robust preference for 12-oxolithocholic acid over 12-oxochenodeoxycholic acid. Phylogenetic analysis identified novel members of the gut microbiome encoding 12?-HSDH. Future reengineering of 12?-HSDH enzymes to preferentially oxidize cholic acid may provide a means to industrially produce the therapeutic bile acid ursodeoxycholic acid. In addition, a cholic acid-specific 12?-HSDH expressed in the gut may be useful for the reduction in deoxycholic acid concentration, a bile acid implicated in cancers of the gastrointestinal (GI) tract.

Dataset Information

Bile Acid 7?-Dehydroxylating Gut Bacteria Secrete Antibiotics that Inhibit Clostridium difficile: Role of Secondary Bile Acids.

Publications

Bile Acid 7α-Dehydroxylating Gut Bacteria Secrete Antibiotics that Inhibit Clostridium difficile: Role of Secondary Bile Acids.

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