Reference - Detail
RRC ID | 41094 |
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Author | Devlin AS, Fischbach MA. |
Title | A biosynthetic pathway for a prominent class of microbiota-derived bile acids. |
Journal | Nat Chem Biol |
Abstract |
The gut bile acid pool is millimolar in concentration, varies widely in composition among individuals and is linked to metabolic disease and cancer. Although these molecules are derived almost exclusively from the microbiota, remarkably little is known about which bacterial species and genes are responsible for their biosynthesis. Here we report a biosynthetic pathway for the second most abundant class in the gut, 3β-hydroxy(iso)-bile acids, whose levels exceed 300 μM in some humans and are absent in others. We show, for the first time, that iso-bile acids are produced by Ruminococcus gnavus, a far more abundant commensal than previously known producers, and that the iso-bile acid pathway detoxifies deoxycholic acid and thus favors the growth of the keystone genus Bacteroides. By revealing the biosynthetic genes for an abundant class of bile acids, our work sets the stage for predicting and rationally altering the composition of the bile acid pool. |
Volume | 11(9) |
Pages | 685-90 |
Published | 2015-9-1 |
DOI | 10.1038/nchembio.1864 |
PII | nchembio.1864 |
PMID | 26192599 |
PMC | PMC4543561 |
MeSH | 3-alpha-Hydroxysteroid Dehydrogenase (B-Specific) / genetics 3-alpha-Hydroxysteroid Dehydrogenase (B-Specific) / metabolism* Bacterial Proteins / genetics Bacterial Proteins / metabolism* Bacteroides / drug effects Bacteroides / growth & development Bile Acids and Salts / biosynthesis* Bile Acids and Salts / chemistry Bile Acids and Salts / metabolism Bile Acids and Salts / pharmacology Escherichia coli / genetics Escherichia coli / metabolism Gene Expression Humans Kinetics Microbial Sensitivity Tests Microbiota / physiology NAD / metabolism NADP / metabolism Recombinant Proteins / genetics Recombinant Proteins / metabolism Ruminococcus / isolation & purification Ruminococcus / metabolism* Stereoisomerism Symbiosis / physiology |
IF | 12.587 |
Times Cited | 102 |
WOS Category | BIOCHEMISTRY & MOLECULAR BIOLOGY |
Resource | |
General Microbes | JCM 10418 |