Outbreak of Murine Infection with <italic toggle="yes">Clostridium difficile</italic> Associated with the Administration of a Pre- and Perinatal Methyl Donor Diet

ABSTRACT Between October 2016 and June 2017, a C57BL/6J mouse colony that was undergoing a pre- and perinatal methyl donor supplementation diet intervention to study the impact of parental nutrition on offspring susceptibility to disease was found to suffer from an epizootic of unexpected deaths. Ne...

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Autores principales:	Theresa Mau, Samantha S. Eckley, Ingrid L. Bergin, Katie Saund, Jason S. Villano, Kimberly C. Vendrov, Evan S. Snitkin, Vincent B. Young, Raymond Yung
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Clostridium difficile mouse outbreak veterinary epidemiology Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/19c8e35455f045948cb484f50caff1d2
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spelling	oai:doaj.org-article:19c8e35455f045948cb484f50caff1d22021-11-15T15:22:22ZOutbreak of Murine Infection with <italic toggle="yes">Clostridium difficile</italic> Associated with the Administration of a Pre- and Perinatal Methyl Donor Diet10.1128/mSphereDirect.00138-192379-5042https://doaj.org/article/19c8e35455f045948cb484f50caff1d22019-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphereDirect.00138-19https://doaj.org/toc/2379-5042ABSTRACT Between October 2016 and June 2017, a C57BL/6J mouse colony that was undergoing a pre- and perinatal methyl donor supplementation diet intervention to study the impact of parental nutrition on offspring susceptibility to disease was found to suffer from an epizootic of unexpected deaths. Necropsy revealed the presence of severe colitis, and further investigation linked these outbreak deaths to a Clostridium difficile strain of ribotype 027 that we term 16N203. C. difficile infection (CDI) is associated with antibiotic use in humans. Current murine models of CDI rely on antibiotic pretreatment to establish clinical phenotypes. In this report, the C. difficile outbreak occurs in F1 mice linked to alterations in the parental diet. The diagnosis of CDI in the affected mice was confirmed by cecal/colonic histopathology, the presence of C. difficile bacteria in fecal/colonic culture, and detection of C. difficile toxins. F1 mice from parents fed the methyl supplementation diet also had significantly reduced survival (P < 0.0001) compared with F1 mice from parents fed the control diet. When we tested the 16N203 outbreak strain in an established mouse model of antibiotic-induced CDI, we confirmed that this strain is pathogenic. Our serendipitous observations from this spontaneous outbreak of C. difficile in association with a pre- and perinatal methyl donor diet suggest the important role that diet may play in host defense and CDI risk factors. IMPORTANCE Clostridium difficile infection (CDI) has become the leading cause of infectious diarrhea in hospitals worldwide, owing its preeminence to the emergence of hyperendemic strains, such as ribotype 027 (RT027). A major CDI risk factor is antibiotic exposure, which alters gut microbiota, resulting in the loss of colonization resistance. Current murine models of CDI also depend on pretreatment of animals with antibiotics to establish disease. The outbreak that we report here is unique in that the CDI occurred in mice with no antibiotic exposure and is associated with a pre- and perinatal methyl supplementation donor diet intervention study. Our investigation subsequently reveals that the outbreak strain that we term 16N203 is an RT027 strain, and this isolated strain is also pathogenic in an established murine model of CDI (with antibiotics). Our report of this spontaneous outbreak offers additional insight into the importance of environmental factors, such as diet, and CDI susceptibility.Theresa MauSamantha S. EckleyIngrid L. BerginKatie SaundJason S. VillanoKimberly C. VendrovEvan S. SnitkinVincent B. YoungRaymond YungAmerican Society for MicrobiologyarticleClostridium difficilemouseoutbreakveterinary epidemiologyMicrobiologyQR1-502ENmSphere, Vol 4, Iss 2 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Clostridium difficile mouse outbreak veterinary epidemiology Microbiology QR1-502
spellingShingle	Clostridium difficile mouse outbreak veterinary epidemiology Microbiology QR1-502 Theresa Mau Samantha S. Eckley Ingrid L. Bergin Katie Saund Jason S. Villano Kimberly C. Vendrov Evan S. Snitkin Vincent B. Young Raymond Yung Outbreak of Murine Infection with <italic toggle="yes">Clostridium difficile</italic> Associated with the Administration of a Pre- and Perinatal Methyl Donor Diet
description	ABSTRACT Between October 2016 and June 2017, a C57BL/6J mouse colony that was undergoing a pre- and perinatal methyl donor supplementation diet intervention to study the impact of parental nutrition on offspring susceptibility to disease was found to suffer from an epizootic of unexpected deaths. Necropsy revealed the presence of severe colitis, and further investigation linked these outbreak deaths to a Clostridium difficile strain of ribotype 027 that we term 16N203. C. difficile infection (CDI) is associated with antibiotic use in humans. Current murine models of CDI rely on antibiotic pretreatment to establish clinical phenotypes. In this report, the C. difficile outbreak occurs in F1 mice linked to alterations in the parental diet. The diagnosis of CDI in the affected mice was confirmed by cecal/colonic histopathology, the presence of C. difficile bacteria in fecal/colonic culture, and detection of C. difficile toxins. F1 mice from parents fed the methyl supplementation diet also had significantly reduced survival (P < 0.0001) compared with F1 mice from parents fed the control diet. When we tested the 16N203 outbreak strain in an established mouse model of antibiotic-induced CDI, we confirmed that this strain is pathogenic. Our serendipitous observations from this spontaneous outbreak of C. difficile in association with a pre- and perinatal methyl donor diet suggest the important role that diet may play in host defense and CDI risk factors. IMPORTANCE Clostridium difficile infection (CDI) has become the leading cause of infectious diarrhea in hospitals worldwide, owing its preeminence to the emergence of hyperendemic strains, such as ribotype 027 (RT027). A major CDI risk factor is antibiotic exposure, which alters gut microbiota, resulting in the loss of colonization resistance. Current murine models of CDI also depend on pretreatment of animals with antibiotics to establish disease. The outbreak that we report here is unique in that the CDI occurred in mice with no antibiotic exposure and is associated with a pre- and perinatal methyl supplementation donor diet intervention study. Our investigation subsequently reveals that the outbreak strain that we term 16N203 is an RT027 strain, and this isolated strain is also pathogenic in an established murine model of CDI (with antibiotics). Our report of this spontaneous outbreak offers additional insight into the importance of environmental factors, such as diet, and CDI susceptibility.
format	article
author	Theresa Mau Samantha S. Eckley Ingrid L. Bergin Katie Saund Jason S. Villano Kimberly C. Vendrov Evan S. Snitkin Vincent B. Young Raymond Yung
author_facet	Theresa Mau Samantha S. Eckley Ingrid L. Bergin Katie Saund Jason S. Villano Kimberly C. Vendrov Evan S. Snitkin Vincent B. Young Raymond Yung
author_sort	Theresa Mau
title	Outbreak of Murine Infection with <italic toggle="yes">Clostridium difficile</italic> Associated with the Administration of a Pre- and Perinatal Methyl Donor Diet
title_short	Outbreak of Murine Infection with <italic toggle="yes">Clostridium difficile</italic> Associated with the Administration of a Pre- and Perinatal Methyl Donor Diet
title_full	Outbreak of Murine Infection with <italic toggle="yes">Clostridium difficile</italic> Associated with the Administration of a Pre- and Perinatal Methyl Donor Diet
title_fullStr	Outbreak of Murine Infection with <italic toggle="yes">Clostridium difficile</italic> Associated with the Administration of a Pre- and Perinatal Methyl Donor Diet
title_full_unstemmed	Outbreak of Murine Infection with <italic toggle="yes">Clostridium difficile</italic> Associated with the Administration of a Pre- and Perinatal Methyl Donor Diet
title_sort	outbreak of murine infection with <italic toggle="yes">clostridium difficile</italic> associated with the administration of a pre- and perinatal methyl donor diet
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/19c8e35455f045948cb484f50caff1d2
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Outbreak of Murine Infection with <italic toggle="yes">Clostridium difficile</italic> Associated with the Administration of a Pre- and Perinatal Methyl Donor Diet

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