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 dehydr...
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Format: | Article |
Language: | English |
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Elsevier
2006-02-01
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Series: | Journal of Lipid Research |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520336269 |
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author | Jason M. Ridlon Dae-Joong Kang Phillip B. Hylemon |
author_facet | Jason M. Ridlon Dae-Joong Kang Phillip B. Hylemon |
author_sort | Jason M. Ridlon |
collection | DOAJ |
description | 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 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. |
first_indexed | 2024-12-21T17:35:52Z |
format | Article |
id | doaj.art-194e5ff4a2814380ba7f884cdbb0b4db |
institution | Directory Open Access Journal |
issn | 0022-2275 |
language | English |
last_indexed | 2024-12-21T17:35:52Z |
publishDate | 2006-02-01 |
publisher | Elsevier |
record_format | Article |
series | Journal of Lipid Research |
spelling | doaj.art-194e5ff4a2814380ba7f884cdbb0b4db2022-12-21T18:55:46ZengElsevierJournal of Lipid Research0022-22752006-02-01472241259Bile salt biotransformations by human intestinal bacteriaJason M. Ridlon0Dae-Joong Kang1Phillip B. Hylemon2Department of Microbiology/Immunology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VADepartment of Microbiology/Immunology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VADepartment of Microbiology/Immunology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VASecondary 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 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.http://www.sciencedirect.com/science/article/pii/S0022227520336269bile acidsdeoxycholic acid7α-dehydroxylationgallstone diseasecolon cancerbile salt hydrolase |
spellingShingle | Jason M. Ridlon Dae-Joong Kang Phillip B. Hylemon Bile salt biotransformations by human intestinal bacteria Journal of Lipid Research bile acids deoxycholic acid 7α-dehydroxylation gallstone disease colon cancer bile salt hydrolase |
title | Bile salt biotransformations by human intestinal bacteria |
title_full | Bile salt biotransformations by human intestinal bacteria |
title_fullStr | Bile salt biotransformations by human intestinal bacteria |
title_full_unstemmed | Bile salt biotransformations by human intestinal bacteria |
title_short | Bile salt biotransformations by human intestinal bacteria |
title_sort | bile salt biotransformations by human intestinal bacteria |
topic | bile acids deoxycholic acid 7α-dehydroxylation gallstone disease colon cancer bile salt hydrolase |
url | http://www.sciencedirect.com/science/article/pii/S0022227520336269 |
work_keys_str_mv | AT jasonmridlon bilesaltbiotransformationsbyhumanintestinalbacteria AT daejoongkang bilesaltbiotransformationsbyhumanintestinalbacteria AT phillipbhylemon bilesaltbiotransformationsbyhumanintestinalbacteria |