Bile salt biotransformations by human intestinal bacteria.
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. The potential exists for altering the bile acid pool by targeting key enzymes in the 7alpha/beta-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.
Ridlon
Jason M
JM
Department of Microbiology/Immunology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA.
Kang
Dae-Joong
DJ
Hylemon
Phillip B
PB
D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D001419:Bacteria / Q000201:enzymology* / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism*; D001711:Biotransformation; D002793:Cholic Acids / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism; D006913:Hydroxysteroid Dehydrogenases / Q000737:chemistry / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000382:microbiology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D017386:Sequence Homology, Amino Acid; D013654:Taurine / Q000378:metabolism
D001647:Bile Acids and Salts; D002793:Cholic Acids; D013654:Taurine; D006913:Hydroxysteroid Dehydrogenases; C031932:7 beta-hydroxysteroid dehydrogenase; C025376:7 alpha-hydroxysteroid dehydrogenase; D000581:Amidohydrolases; C023154:choloylglycine hydrolase; D006862:Hydrogen Sulfide