Bile salt biotransformations by human intestinal bacteria

Jason M. Ridlon, Dae Joong Kang, Phillip B. Hylemon

Research output: Contribution to journalReview article

Abstract

Secondary bile acids, produced solely by intestinal bacteria, can accumulate to high levels in the enterohepatic circulation of some individuals and may contribute to the pathogenesis of colon cancer, gallstones, and other gastrointestinal (GI) diseases. Bile salt hydrolysis and hydroxy group dehydrogenation reactions are carried out by a broad spectrum of intestinal anaerobic bacteria, whereas bile acid 7-dehydroxylation appears restricted to a limited number of intestinal anaerobes representing a small fraction of the total colonic flora. Microbial enzymes modifying bile salts differ between species with respect to pH optima, enzyme kinetics, substrate specificity, cellular location, and possibly physiological function. Crystallization, site-directed mutagenesis, and comparisons of protein secondary structure have provided insight into the mechanisms of several bile acid-biotransforming enzymatic reactions. Molecular cloning of genes encoding bile salt-modifying enzymes has facilitated the understanding of the genetic organization of these pathways and is a means of developing probes for the detection of bile salt-modifying bacteria.jlr The potential exists for altering the bile acid pool by targeting key enzymes in the 7α/β-dehydroxylation pathway through the development of pharmaceuticals or sequestering bile acids biologically in probiotic bacteria, which may result in their effective removal from the host after excretion.

Original languageEnglish (US)
Pages (from-to)241-259
Number of pages19
JournalJournal of Lipid Research
Volume47
Issue number2
DOIs
StatePublished - Feb 1 2006
Externally publishedYes

Keywords

  • 7α-dehydroxylation
  • Bile acids
  • Bile salt hydrolase
  • Colon cancer
  • Deoxycholic acid
  • Gallstone disease
  • Hydrogen sulfide
  • Hydroxysteroid dehydrogenase
  • Probiotics

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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