Functional Intestinal Bile Acid 7α-Dehydroxylation by Clostridium scindens Associated with Protection from Clostridium difficile Infection in a Gnotobiotic Mouse Model

Studer, Nicolas; Desharnais, Lyne; Beutler, Markus; Brugiroux, Sandrine; Terrazos Miani, Miguel Angel; Menin, Laure; Schürch, Christian; McCoy, Kathy D.; Kuehne, Sarah A.; Minton, Nigel P.; Stecher, Bärbel; Bernier-Latmani, Rizlan; Hapfelmeier, Siegfried Hektor (2016). Functional Intestinal Bile Acid 7α-Dehydroxylation by Clostridium scindens Associated with Protection from Clostridium difficile Infection in a Gnotobiotic Mouse Model. Frontiers in cellular and infection microbiology, 6(191), p. 191. Frontiers 10.3389/fcimb.2016.00191

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Bile acids, important mediators of lipid absorption, also act as hormone-like regulators and as antimicrobial molecules. In all these functions their potency is modulated by a variety of chemical modifications catalyzed by bacteria of the healthy gut microbiota, generating a complex variety of secondary bile acids. Intestinal commensal organisms are well-adapted to normal concentrations of bile acids in the gut. In contrast, physiological concentrations of the various intestinal bile acid species play an important role in the resistance to intestinal colonization by pathogens such as Clostridium difficile. Antibiotic therapy can perturb the gut microbiota and thereby impair the production of protective secondary bile acids. The most important bile acid transformation is 7α-dehydroxylation, producing deoxycholic acid (DCA) and lithocholic acid (LCA). The enzymatic pathway carrying out 7α-dehydroxylation is restricted to a narrow phylogenetic group of commensal bacteria, the best-characterized of which is Clostridium scindens. Like many other intestinal commensal species, 7-dehydroxylating bacteria are understudied in vivo. Conventional animals contain variable and uncharacterized indigenous 7α-dehydroxylating organisms that cannot be selectively removed, making controlled colonization with a specific strain in the context of an undisturbed microbiota unfeasible. In the present study, we used a recently established, standardized gnotobiotic mouse model that is stably associated with a simplified murine 12-species “oligo-mouse microbiota” (Oligo-MM12). It is representative of the major murine intestinal bacterial phyla, but is deficient for 7α-dehydroxylation. We find that the Oligo-MM12 consortium carries out bile acid deconjugation, a prerequisite for 7α-dehydroxylation, and confers no resistance to C. difficile infection (CDI). Amendment of Oligo-MM12 with C. scindens normalized the large intestinal bile acid composition by reconstituting 7α-dehydroxylation. These changes had only minor effects on the composition of the native Oligo-MM12, but significantly decreased early large intestinal C. difficile colonization and pathogenesis. The delayed pathogenesis of C. difficile in C. scindens-colonized mice was associated with breakdown of cecal microbial bile acid transformation.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Research
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Gastroenterology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie

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

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Studer, Nicolas; Terrazos Miani, Miguel Angel; Schürch, Christian; McCoy, Kathleen and Hapfelmeier, Siegfried Hektor

Subjects:

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

ISSN:

2235-2988

Publisher:

Frontiers

Language:

English

Submitter:

Siegfried Hektor Hapfelmeier-Balmer

Date Deposited:

21 Dec 2016 14:42

Last Modified:

26 Mar 2018 11:18

Publisher DOI:

10.3389/fcimb.2016.00191

PubMed ID:

28066726

BORIS DOI:

10.7892/boris.91993

URI:

https://boris.unibe.ch/id/eprint/91993

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