Document Detail

Systemic gut microbial modulation of bile acid metabolism in host tissue compartments.
MedLine Citation:
PMID:  20837534     Owner:  NLM     Status:  MEDLINE    
We elucidate the detailed effects of gut microbial depletion on the bile acid sub-metabolome of multiple body compartments (liver, kidney, heart, and blood plasma) in rats. We use a targeted ultra-performance liquid chromatography with time of flight mass-spectrometry assay to characterize the differential primary and secondary bile acid profiles in each tissue and show a major increase in the proportion of taurine-conjugated bile acids in germ-free (GF) and antibiotic (streptomycin/penicillin)-treated rats. Although conjugated bile acids dominate the hepatic profile (97.0 ± 1.5%) of conventional animals, unconjugated bile acids comprise the largest proportion of the total measured bile acid profile in kidney (60.0 ± 10.4%) and heart (53.0 ± 18.5%) tissues. In contrast, in the GF animal, taurine-conjugated bile acids (especially taurocholic acid and tauro-β-muricholic acid) dominated the bile acid profiles (liver: 96.0 ± 14.5%; kidney: 96 ± 1%; heart: 93 ± 1%; plasma: 93.0 ± 2.3%), with unconjugated and glycine-conjugated species representing a small proportion of the profile. Higher free taurine levels were found in GF livers compared with the conventional liver (5.1-fold; P < 0.001). Bile acid diversity was also lower in GF and antibiotic-treated tissues compared with conventional animals. Because bile acids perform important signaling functions, it is clear that these chemical communication networks are strongly influenced by microbial activities or modulation, as evidenced by farnesoid X receptor-regulated pathway transcripts. The presence of specific microbial bile acid co-metabolite patterns in peripheral tissues (including heart and kidney) implies a broader signaling role for these compounds and emphasizes the extent of symbiotic microbial influences in mammalian homeostasis.
Jonathan R Swann; Elizabeth J Want; Florian M Geier; Konstantina Spagou; Ian D Wilson; James E Sidaway; Jeremy K Nicholson; Elaine Holmes
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-13
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  108 Suppl 1     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-03-16     Completed Date:  2011-05-17     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4523-30     Citation Subset:  IM    
Biomolecular Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College, London SW7 2AZ, United Kingdom.
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MeSH Terms
Anti-Bacterial Agents / pharmacology
Bacteria / drug effects,  genetics,  metabolism*
Bile Acids and Salts / blood,  metabolism*
Chromatography, High Pressure Liquid
Gastrointestinal Tract / microbiology*
Heart / microbiology
Kidney / metabolism*,  microbiology
Liver / metabolism*,  microbiology
Mass Spectrometry
Metagenome / genetics*
Myocardium / metabolism*
Receptors, Cytoplasmic and Nuclear / metabolism
Signal Transduction / genetics,  physiology
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/Bile Acids and Salts; 0/Receptors, Cytoplasmic and Nuclear; 0/farnesoid X-activated receptor

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