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 (2020). Biogeography of microbial bile acid transformations along the murine gut. Journal of lipid research, 61(11), pp. 1450-1463. American Society for Biochemistry and Molecular Biology ASBMB 10.1194/jlr.RA120001021

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Research
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Studer, Nicolas; Dong, Yuan; Notter Dias, Matheus and Hapfelmeier, Siegfried Hektor

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0022-2275

Publisher:

American Society for Biochemistry and Molecular Biology ASBMB

Language:

English

Submitter:

Siegfried Hektor Hapfelmeier-Balmer

Date Deposited:

13 Jan 2021 16:13

Last Modified:

13 Jan 2021 16:13

Publisher DOI:

10.1194/jlr.RA120001021

PubMed ID:

32661017

Uncontrolled Keywords:

Cyp7a1 Oligo-MM12 Sult2a8 biosynthesis farnesoid X receptor fibroblast growth factor 15 metabolome microbiome proteomics

BORIS DOI:

10.48350/150217

URI:

https://boris.unibe.ch/id/eprint/150217

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