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Titre du document / Document title

A human gut ecosystem protects against C. difficile disease by targeting TcdA

Auteur(s) / Author(s)

Martz Sarah Lynn (1) ; Guzman-Rodriguez Mabel (1) ; He Shu-Mei (1) ; Noordhof Curtis (1) ; Hurlbut David John (2) ; Gloor Gregory Brian (3) ; Carlucci Christian (4) ; Weese Scott (4) ; Allen-Vercoe Emma (4) ; Sun Jun (5) ; Claud Erika Chiong (6) ; Petrof Elaine Olga (1) ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

(1) Division of Infectious Diseases/GI Diseases Research Unit Wing, Department of Medicine, Kingston General Hospital, Queen’s University, ON, Kingston, Canada
(2) Department of Pathology and Molecular Medicine, Queen’s University, ON, Kingston, Canada
(3) Department of Biochemistry, University of Western Ontario, ON, London, Canada
(4) Department of Molecular and Cellular Biology, University of Guelph, ON, Guelph, Canada
(5) Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois at Chicago, IL, Chicago, USA
(6) Departments of Pediatrics and Medicine, University of Chicago, IL, Chicago, USA

Résumé / Abstract

Background A defined Microbial Ecosystem Therapeutic (MET-1, or “RePOOPulate”) derived from the feces of a healthy volunteer can cure recurrent C. difficile infection (rCDI) in humans. The mechanisms of action whereby healthy microbiota protect against rCDI remain unclear. Since C. difficile toxins are largely responsible for the disease pathology of CDI, we hypothesized that MET-1 exerts its protective effects by inhibiting the effects of these toxins on the host.MethodsA combination of in vivo (antibiotic-associated mouse model of C. difficile colitis, mouse ileal loop model) and in vitro models (FITC-phalloidin staining, F actin Western blots and apoptosis assay in Caco2 cells, transepithelial electrical resistance measurements in T84 cells) were employed.ResultsMET-1 decreased both local and systemic inflammation in infection and decreased both the cytotoxicity and the amount of TcdA detected in stool, without an effect on C.difficile viability. MET-1 protected against TcdA-mediated damage in a murine ileal loop model. MET-1 protected the integrity of the cytoskeleton in cells treated with purified TcdA, as indicated by FITC-phalloidin staining, F:G actin assays and preservation of transepithelial electrical resistance. Finally, co-incubation of MET-1 with purified TcdA resulted in decreased detectable TcdA by Western blot analysis.ConclusionsMET-1 intestinal microbiota confers protection against C. difficile and decreases C. difficile-mediated inflammation through its protective effects against C. difficile toxins, including enhancement of host barrier function and degradation of TcdA. The effect of MET-1 on C. difficile viability seems to offer little, if any, contribution to its protective effects on the host.

Revue / Journal Title

Journal of gastroenterology    ISSN  1435-5922 

Source / Source

2017, vol. 52, no4, pp. 452-465 [14 page(s) (article)]

Langue / Language

Anglais

Editeur / Publisher

Springer, Heidelberg, ALLEMAGNE  (199?) (Revue)

Mots-clés d'auteur / Author Keywords

Microbiota

;

C. difficile

;

TcdA

;

Localisation / Location

35400063179122.0003

Japanese Society of Gastroenterology, 2017
Nº notice refdoc (ud4) : 30429779



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