Submitted on October 11, 2005
Revised on November 17, 2005
Accepted on November 18, 2005
Bile salt biotransformation by human intestinal bacteria
Jason M. Ridlon, Dae-Joong Kang, and Phillip B. Hylemon
Microbiology/Immunology, Virginia Commonwealth University, Richmond, VA 23298-0678
Corresponding Author: pbhylemo{at}vcu.edu
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 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 understanding of the genetic organization of these pathways and a means of developing probes for detection of bile salt modifying bacteria. The potential exists for altering the bile acid pool by targeting key enzymes in the 7
/
-dehydroxylation pathway through development of pharmaceuticals or sequestering bile acids biologically in probiotic bacteria which may result in their effective removal from host following excretion.
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