Metabolism of oxo-bile acids and characterization of recombinant 12α- hydroxysteroid dehydrogenases from bile acid 7α-dehydroxylating human gut bacteria

Heidi Doden, Lina A. Sallam, Saravanan Devendran, Lindsey Ly, Greta Doden, Steven L. Daniel, João M.P. Alves, Jason M. Ridlon

Research output: Contribution to journalArticlepeer-review

Abstract

Bile acids are important cholesterol-derived nutrient signaling hormones, synthesized in the liver, that act as detergents to solubilize dietary lipids. Bile acid 7α- 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 7α-hydroxysteroid dehydrogenase (HSDH) activity, which reduces 7-oxo-bile acids generated by other gut bacteria. 3α-HSDH has an important enzymatic activity in the bile acid 7α-dehydroxylation pathway. 12α-HSDH activity has been reported for the low-activity bile acid 7α-dehydroxylating bacterium Clostridium leptum; however, this activity has not been reported for high-activity bile acid 7α- dehydroxylating bacteria, such as Clostridium scindens, Clostridium hylemonae, and Clostridium hiranonis. Here, we demonstrate that these strains express bile acid 12α-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 12α-HSDH is widespread among Firmicutes, Actinobacteria in the Coriobacteriaceae family, and human gut Archaea.

Original languageEnglish (US)
Article numbere00235-18
JournalApplied and environmental microbiology
Volume84
Issue number10
DOIs
StatePublished - May 1 2018

Keywords

  • 12α-hydroxysteroid dehydrogenase
  • Bile acid 7α-dehydroxylation
  • Cholic acid
  • Clostridium hiranonis
  • Clostridium hylemonae
  • Clostridium scindens
  • Deoxycholic acid
  • Human gut bacteria
  • Oxo-bile acids

ASJC Scopus subject areas

  • Biotechnology
  • Food Science
  • Applied Microbiology and Biotechnology
  • Ecology

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