Systemic gut microbial modulation of bile acid metabolism in host tissue compartments.
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.
Swann
Jonathan R
JR
Biomolecular Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College, London SW7 2AZ, United Kingdom.
Want
Elizabeth J
EJ
Geier
Florian M
FM
Spagou
Konstantina
K
Wilson
Ian D
ID
Sidaway
James E
JE
Nicholson
Jeremy K
JK
Holmes
Elaine
E
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000097:blood / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D041981:Gastrointestinal Tract / Q000382:microbiology*; D006321:Heart / Q000382:microbiology; D007668:Kidney / Q000378:metabolism* / Q000382:microbiology; D008099:Liver / Q000378:metabolism* / Q000382:microbiology; D013058:Mass Spectrometry; D054892:Metagenome / Q000235:genetics*; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013559:Symbiosis; D000099150:Receptor, Farnesoid X-Activated
D000900:Anti-Bacterial Agents; D001647:Bile Acids and Salts; D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated