The Gut Microbiota Is Associated with Clearance of <named-content content-type="genus-species">Clostridium difficile</named-content> Infection Independent of Adaptive Immunity

ABSTRACT Clostridium (Clostridioides) difficile, a Gram-positive, anaerobic bacterium, is the leading single cause of nosocomial infections in the United States. A major risk factor for Clostridium difficile infection (CDI) is prior exposure to antibiotics, as they increase susceptibility to CDI by...

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Autores principales:	Jhansi L. Leslie, Kimberly C. Vendrov, Matthew L. Jenior, Vincent B. Young
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Clostridium difficile adaptive immunity colonization resistance intestinal colonization microbiota Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/d5acd46ecdab471fabdd0ee27a9c43c3
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spelling	oai:doaj.org-article:d5acd46ecdab471fabdd0ee27a9c43c32021-11-15T15:22:05ZThe Gut Microbiota Is Associated with Clearance of <named-content content-type="genus-species">Clostridium difficile</named-content> Infection Independent of Adaptive Immunity10.1128/mSphereDirect.00698-182379-5042https://doaj.org/article/d5acd46ecdab471fabdd0ee27a9c43c32019-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphereDirect.00698-18https://doaj.org/toc/2379-5042ABSTRACT Clostridium (Clostridioides) difficile, a Gram-positive, anaerobic bacterium, is the leading single cause of nosocomial infections in the United States. A major risk factor for Clostridium difficile infection (CDI) is prior exposure to antibiotics, as they increase susceptibility to CDI by altering the membership of the microbial community enabling colonization. The importance of the gut microbiota in providing protection from CDI is underscored by the reported 80 to 90% success rate of fecal microbial transplants in treating recurrent infections. Adaptive immunity, specifically humoral immunity, is also sufficient to protect from both acute and recurrent CDI. However, the role of the adaptive immune system in mediating clearance of C. difficile has yet to be resolved. Using murine models of CDI, we found that adaptive immunity is dispensable for clearance of C. difficile. However, random forest analysis using only two members of the resident bacterial community correctly identified animals that would go on to clear the infection with 66.7% accuracy. These findings indicate that the indigenous gut microbiota independent of adaptive immunity facilitates clearance of C. difficile from the murine gastrointestinal tract. IMPORTANCE Clostridium difficile infection is a major cause of morbidity and mortality in hospitalized patients in the United States. Currently, the role of the adaptive immune response in modulating levels of C. difficile colonization is unresolved. This work suggests that the indigenous gut microbiota is a main factor that promotes clearance of C. difficile from the GI tract. Our results show that clearance of C. difficile can occur without contributions from the adaptive immune response. This study also has implications for the design of preclinical studies testing the efficacy of vaccines on clearance of bacterial pathogens, as inherent differences in the baseline community structure of animals may bias findings.Jhansi L. LeslieKimberly C. VendrovMatthew L. JeniorVincent B. YoungAmerican Society for MicrobiologyarticleClostridium difficileadaptive immunitycolonization resistanceintestinal colonizationmicrobiotaMicrobiologyQR1-502ENmSphere, Vol 4, Iss 1 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Clostridium difficile adaptive immunity colonization resistance intestinal colonization microbiota Microbiology QR1-502
spellingShingle	Clostridium difficile adaptive immunity colonization resistance intestinal colonization microbiota Microbiology QR1-502 Jhansi L. Leslie Kimberly C. Vendrov Matthew L. Jenior Vincent B. Young The Gut Microbiota Is Associated with Clearance of <named-content content-type="genus-species">Clostridium difficile</named-content> Infection Independent of Adaptive Immunity
description	ABSTRACT Clostridium (Clostridioides) difficile, a Gram-positive, anaerobic bacterium, is the leading single cause of nosocomial infections in the United States. A major risk factor for Clostridium difficile infection (CDI) is prior exposure to antibiotics, as they increase susceptibility to CDI by altering the membership of the microbial community enabling colonization. The importance of the gut microbiota in providing protection from CDI is underscored by the reported 80 to 90% success rate of fecal microbial transplants in treating recurrent infections. Adaptive immunity, specifically humoral immunity, is also sufficient to protect from both acute and recurrent CDI. However, the role of the adaptive immune system in mediating clearance of C. difficile has yet to be resolved. Using murine models of CDI, we found that adaptive immunity is dispensable for clearance of C. difficile. However, random forest analysis using only two members of the resident bacterial community correctly identified animals that would go on to clear the infection with 66.7% accuracy. These findings indicate that the indigenous gut microbiota independent of adaptive immunity facilitates clearance of C. difficile from the murine gastrointestinal tract. IMPORTANCE Clostridium difficile infection is a major cause of morbidity and mortality in hospitalized patients in the United States. Currently, the role of the adaptive immune response in modulating levels of C. difficile colonization is unresolved. This work suggests that the indigenous gut microbiota is a main factor that promotes clearance of C. difficile from the GI tract. Our results show that clearance of C. difficile can occur without contributions from the adaptive immune response. This study also has implications for the design of preclinical studies testing the efficacy of vaccines on clearance of bacterial pathogens, as inherent differences in the baseline community structure of animals may bias findings.
format	article
author	Jhansi L. Leslie Kimberly C. Vendrov Matthew L. Jenior Vincent B. Young
author_facet	Jhansi L. Leslie Kimberly C. Vendrov Matthew L. Jenior Vincent B. Young
author_sort	Jhansi L. Leslie
title	The Gut Microbiota Is Associated with Clearance of <named-content content-type="genus-species">Clostridium difficile</named-content> Infection Independent of Adaptive Immunity
title_short	The Gut Microbiota Is Associated with Clearance of <named-content content-type="genus-species">Clostridium difficile</named-content> Infection Independent of Adaptive Immunity
title_full	The Gut Microbiota Is Associated with Clearance of <named-content content-type="genus-species">Clostridium difficile</named-content> Infection Independent of Adaptive Immunity
title_fullStr	The Gut Microbiota Is Associated with Clearance of <named-content content-type="genus-species">Clostridium difficile</named-content> Infection Independent of Adaptive Immunity
title_full_unstemmed	The Gut Microbiota Is Associated with Clearance of <named-content content-type="genus-species">Clostridium difficile</named-content> Infection Independent of Adaptive Immunity
title_sort	gut microbiota is associated with clearance of <named-content content-type="genus-species">clostridium difficile</named-content> infection independent of adaptive immunity
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/d5acd46ecdab471fabdd0ee27a9c43c3
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The Gut Microbiota Is Associated with Clearance of <named-content content-type="genus-species">Clostridium difficile</named-content> Infection Independent of Adaptive Immunity

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