Biogeography of microbial bile acid transformations along the murine gut

Marion, Solenne; Desharnais, Lyne; Studer, Nicolas; Dong, Yuan; Notter, Matheus D.; Poudel, Suresh; Menin, Laure; Janowczyk, Andrew; Hettich, Robert L.; Hapfelmeier, Siegfried; Bernier-Latmani, Rizlan

doi:10.1194/jlr.ra120001021

Biogeography of microbial bile acid transformations along the murine gut

Journal Article · Mon Jan 04 00:00:00 EST 2021 · Journal of Lipid Research

DOI:https://doi.org/10.1194/jlr.ra120001021· OSTI ID:1813254

^[1]; Desharnais, Lyne ^[1]; Studer, Nicolas ^[2]; Dong, Yuan ^[2]; Notter, Matheus D. ^[2]; Poudel, Suresh ^[3]; Menin, Laure ^[1]; Janowczyk, Andrew ^[4]; ^[3]; Hapfelmeier, Siegfried ^[2]; ^[1]

Ecole Polytechnique Federale Lausanne (Switzerland)
Univ. of Bern (Switzerland)
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Swiss Inst. of Bioformatics, Lausanne (Switzerland)

Bile acids, which are synthesized from cholesterol by the liver, are chemically transformed along the intestinal tract by the gut microbiota, and the products of these transformations signal through host receptors, affecting overall host health. These transformations include bile acid deconjugation, oxidation, and 7α-dehydroxylation. An understanding of the biogeography of bile acid transformations in the gut is critical because deconjugation is a prerequisite for 7α-dehydroxylation and because most gut microorganisms harbor bile acid transformation capacity. Here, we used a coupled metabolomic and metaproteomic approach to probe in vivo activity of the gut microbial community in a gnotobiotic mouse model. Results revealed the involvement of Clostridium scindens in 7α-dehydroxylation, of the genera Muribaculum and Bacteroides in deconjugation, and of six additional organisms in oxidation (the genera Clostridium, Muribaculum, Bacteroides, Bifidobacterium, Acutalibacter, and Akkermansia). Furthermore, the bile acid profile in mice with a more complex microbiota, a dysbiosed microbiota, or no microbiota was considered. For instance, conventional mice harbor a large diversity of bile acids, but treatment with an antibiotic such as clindamycin results in the complete inhibition of 7α-dehydroxylation, underscoring the strong inhibition of organisms that are capable of carrying out this process by this compound. Finally, a comparison of the hepatic bile acid pool size as a function of microbiota revealed that a reduced microbiota affects host signaling but not necessarily bile acid synthesis. In this study, bile acid transformations were mapped to the associated active microorganisms, offering a systematic characterization of the relationship between microbiota and bile acid composition.

View Accepted Manuscript (DOE)

Research Organization:: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)

Sponsoring Organization:: Swiss National Science Foundation (SNSF); USDOE

Grant/Contract Number:: AC05-00OR22725

OSTI ID:: 1813254

Journal Information:: Journal of Lipid Research, Journal Name: Journal of Lipid Research Journal Issue: 11 Vol. 61; ISSN 0022-2275

Publisher:: American Society for Biochemistry and Molecular BiologyCopyright Statement

Country of Publication:: United States

Language:: English

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