In vitro and in vivo characterization of Clostridium scindens bile acid transformations.

Marion, Solenne; Studer, Nicolas; Desharnais, Lyne; Menin, Laure; Escrig, Stéphane; Meibom, Anders; Hapfelmeier, Siegfried Hektor; Bernier-Latmani, Rizlan (2019). In vitro and in vivo characterization of Clostridium scindens bile acid transformations. Gut microbes, 10(4), pp. 481-503. Taylor & Francis 10.1080/19490976.2018.1549420

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The human gut hosts trillions of microorganisms that exert a profound influence on human biology. Gut bacteria communicate with their host by secreting small molecules that can signal to distant organs in the body. Bile acids are one class of these signaling molecules, synthesized by the host and chemically transformed by the gut microbiota. Among bile acid metabolizers, bile acid 7-dehydroxylating bacteria are commensals of particular importance as they carry out the 7-dehydroxylation of liver-derived primary bile acids to 7-dehydroxylated bile acids. The latter represents a major fraction of the secondary bile acid pool. The microbiology of this group of gut microorganisms is understudied and warrants more attention. Here, we detail the bile acid transformations carried out by the 7-dehydroxylating bacterium Clostridium scindens in vitro and in vivo. In vitro, C. scindens exhibits not only 7α-dehydroxylating capabilities but also, the ability to oxidize other hydroxyl groups and reduce ketone groups in primary and secondary bile acids. This study revealed 12-oxolithocholic acid as a major transient product in the 7α-dehydroxylation of cholic acid. Furthermore, the in vivo study included complementing a gnotobiotic mouse line (devoid of the ability to 7-dehydroxylate bile acids) with C. scindens and investigating its colonization dynamics and bile acid transformations. Using NanoSIMS (Nanoscale Secondary Ion Mass Spectrometry), we demonstrate that the large intestine constitutes a niche for C. scindens, where it efficiently 7-dehydroxylates cholic acid to deoxycholic acid. Overall, this work reveals a novel transient species during 7-dehydroxylation as well as provides direct evidence for the colonization and growth of 7-dehydroxylating bacteria in the large intestine.

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 and Hapfelmeier, Siegfried Hektor

Subjects:

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

ISSN:

1949-0976

Publisher:

Taylor & Francis

Funders:

[42] Schweizerischer Nationalfonds
[42] Schweizerischer Nationalfonds

Language:

English

Submitter:

Siegfried Hektor Hapfelmeier-Balmer

Date Deposited:

21 Feb 2019 14:06

Last Modified:

23 Oct 2019 00:25

Publisher DOI:

10.1080/19490976.2018.1549420

PubMed ID:

30589376

Uncontrolled Keywords:

12-oxo bile acids 7α-dehydroxylation pathway Bile salts clostridium commensal bacteria deoxycholic acid (DCA) gut ecology intestinal colonization lithocholic acid (LCA) stable isotopes

BORIS DOI:

10.7892/boris.125150

URI:

https://boris.unibe.ch/id/eprint/125150

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