The Proton Pump Inhibitor Omeprazole Does Not Promote <named-content content-type="genus-species">Clostridioides difficile</named-content> Colonization in a Murine Model

ABSTRACT Proton pump inhibitor (PPI) use has been associated with microbiota alterations and susceptibility to Clostridioides difficile infections (CDIs) in humans. We assessed how PPI treatment alters the fecal microbiota and whether treatment promotes CDIs in a mouse model. Mice receiving a PPI tr...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Sarah Tomkovich, Nicholas A. Lesniak, Yuan Li, Lucas Bishop, Madison J. Fitzgerald, Patrick D. Schloss
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	16S rRNA gene Clostridioides difficile Clostridium difficile colonization resistance infection microbial ecology Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/768b23978e1940aba419fd52048f7eaa
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:768b23978e1940aba419fd52048f7eaa
record_format	dspace
spelling	oai:doaj.org-article:768b23978e1940aba419fd52048f7eaa2021-11-15T15:22:24ZThe Proton Pump Inhibitor Omeprazole Does Not Promote <named-content content-type="genus-species">Clostridioides difficile</named-content> Colonization in a Murine Model10.1128/mSphere.00693-192379-5042https://doaj.org/article/768b23978e1940aba419fd52048f7eaa2019-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00693-19https://doaj.org/toc/2379-5042ABSTRACT Proton pump inhibitor (PPI) use has been associated with microbiota alterations and susceptibility to Clostridioides difficile infections (CDIs) in humans. We assessed how PPI treatment alters the fecal microbiota and whether treatment promotes CDIs in a mouse model. Mice receiving a PPI treatment were gavaged with 40 mg of omeprazole per kg of body weight during a 7-day pretreatment phase, the day of C. difficile challenge, and the following 9 days. We found that mice treated with omeprazole were not colonized by C. difficile. When omeprazole treatment was combined with a single clindamycin treatment, one cage of mice remained resistant to C. difficile colonization, while the other cage was colonized. Treating mice with only clindamycin followed by challenge resulted in C. difficile colonization. 16S rRNA gene sequencing analysis revealed that omeprazole had minimal impact on the structure of the murine microbiota throughout the 16 days of omeprazole exposure. These results suggest that omeprazole treatment alone is not sufficient to disrupt microbiota resistance to C. difficile infection in mice that are normally resistant in the absence of antibiotic treatment. IMPORTANCE Antibiotics are the primary risk factor for Clostridioides difficile infections (CDIs), but other factors may also increase a person’s risk. In epidemiological studies, proton pump inhibitor (PPI) use has been associated with CDI incidence and recurrence. PPIs have also been associated with alterations in the human intestinal microbiota in observational and interventional studies. We evaluated the effects of the PPI omeprazole on the structure of the murine intestinal microbiota and its ability to disrupt colonization resistance to C. difficile. We found omeprazole treatment had minimal impact on the murine fecal microbiota and did not promote C. difficile colonization. Further studies are needed to determine whether other factors contribute to the association between PPIs and CDIs seen in humans or whether aspects of murine physiology may limit its utility to test these types of hypotheses.Sarah TomkovichNicholas A. LesniakYuan LiLucas BishopMadison J. FitzgeraldPatrick D. SchlossAmerican Society for Microbiologyarticle16S rRNA geneClostridioides difficileClostridium difficilecolonization resistanceinfectionmicrobial ecologyMicrobiologyQR1-502ENmSphere, Vol 4, Iss 6 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	16S rRNA gene Clostridioides difficile Clostridium difficile colonization resistance infection microbial ecology Microbiology QR1-502
spellingShingle	16S rRNA gene Clostridioides difficile Clostridium difficile colonization resistance infection microbial ecology Microbiology QR1-502 Sarah Tomkovich Nicholas A. Lesniak Yuan Li Lucas Bishop Madison J. Fitzgerald Patrick D. Schloss The Proton Pump Inhibitor Omeprazole Does Not Promote <named-content content-type="genus-species">Clostridioides difficile</named-content> Colonization in a Murine Model
description	ABSTRACT Proton pump inhibitor (PPI) use has been associated with microbiota alterations and susceptibility to Clostridioides difficile infections (CDIs) in humans. We assessed how PPI treatment alters the fecal microbiota and whether treatment promotes CDIs in a mouse model. Mice receiving a PPI treatment were gavaged with 40 mg of omeprazole per kg of body weight during a 7-day pretreatment phase, the day of C. difficile challenge, and the following 9 days. We found that mice treated with omeprazole were not colonized by C. difficile. When omeprazole treatment was combined with a single clindamycin treatment, one cage of mice remained resistant to C. difficile colonization, while the other cage was colonized. Treating mice with only clindamycin followed by challenge resulted in C. difficile colonization. 16S rRNA gene sequencing analysis revealed that omeprazole had minimal impact on the structure of the murine microbiota throughout the 16 days of omeprazole exposure. These results suggest that omeprazole treatment alone is not sufficient to disrupt microbiota resistance to C. difficile infection in mice that are normally resistant in the absence of antibiotic treatment. IMPORTANCE Antibiotics are the primary risk factor for Clostridioides difficile infections (CDIs), but other factors may also increase a person’s risk. In epidemiological studies, proton pump inhibitor (PPI) use has been associated with CDI incidence and recurrence. PPIs have also been associated with alterations in the human intestinal microbiota in observational and interventional studies. We evaluated the effects of the PPI omeprazole on the structure of the murine intestinal microbiota and its ability to disrupt colonization resistance to C. difficile. We found omeprazole treatment had minimal impact on the murine fecal microbiota and did not promote C. difficile colonization. Further studies are needed to determine whether other factors contribute to the association between PPIs and CDIs seen in humans or whether aspects of murine physiology may limit its utility to test these types of hypotheses.
format	article
author	Sarah Tomkovich Nicholas A. Lesniak Yuan Li Lucas Bishop Madison J. Fitzgerald Patrick D. Schloss
author_facet	Sarah Tomkovich Nicholas A. Lesniak Yuan Li Lucas Bishop Madison J. Fitzgerald Patrick D. Schloss
author_sort	Sarah Tomkovich
title	The Proton Pump Inhibitor Omeprazole Does Not Promote <named-content content-type="genus-species">Clostridioides difficile</named-content> Colonization in a Murine Model
title_short	The Proton Pump Inhibitor Omeprazole Does Not Promote <named-content content-type="genus-species">Clostridioides difficile</named-content> Colonization in a Murine Model
title_full	The Proton Pump Inhibitor Omeprazole Does Not Promote <named-content content-type="genus-species">Clostridioides difficile</named-content> Colonization in a Murine Model
title_fullStr	The Proton Pump Inhibitor Omeprazole Does Not Promote <named-content content-type="genus-species">Clostridioides difficile</named-content> Colonization in a Murine Model
title_full_unstemmed	The Proton Pump Inhibitor Omeprazole Does Not Promote <named-content content-type="genus-species">Clostridioides difficile</named-content> Colonization in a Murine Model
title_sort	proton pump inhibitor omeprazole does not promote <named-content content-type="genus-species">clostridioides difficile</named-content> colonization in a murine model
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/768b23978e1940aba419fd52048f7eaa
work_keys_str_mv	AT sarahtomkovich theprotonpumpinhibitoromeprazoledoesnotpromotenamedcontentcontenttypegenusspeciesclostridioidesdifficilenamedcontentcolonizationinamurinemodel AT nicholasalesniak theprotonpumpinhibitoromeprazoledoesnotpromotenamedcontentcontenttypegenusspeciesclostridioidesdifficilenamedcontentcolonizationinamurinemodel AT yuanli theprotonpumpinhibitoromeprazoledoesnotpromotenamedcontentcontenttypegenusspeciesclostridioidesdifficilenamedcontentcolonizationinamurinemodel AT lucasbishop theprotonpumpinhibitoromeprazoledoesnotpromotenamedcontentcontenttypegenusspeciesclostridioidesdifficilenamedcontentcolonizationinamurinemodel AT madisonjfitzgerald theprotonpumpinhibitoromeprazoledoesnotpromotenamedcontentcontenttypegenusspeciesclostridioidesdifficilenamedcontentcolonizationinamurinemodel AT patrickdschloss theprotonpumpinhibitoromeprazoledoesnotpromotenamedcontentcontenttypegenusspeciesclostridioidesdifficilenamedcontentcolonizationinamurinemodel AT sarahtomkovich protonpumpinhibitoromeprazoledoesnotpromotenamedcontentcontenttypegenusspeciesclostridioidesdifficilenamedcontentcolonizationinamurinemodel AT nicholasalesniak protonpumpinhibitoromeprazoledoesnotpromotenamedcontentcontenttypegenusspeciesclostridioidesdifficilenamedcontentcolonizationinamurinemodel AT yuanli protonpumpinhibitoromeprazoledoesnotpromotenamedcontentcontenttypegenusspeciesclostridioidesdifficilenamedcontentcolonizationinamurinemodel AT lucasbishop protonpumpinhibitoromeprazoledoesnotpromotenamedcontentcontenttypegenusspeciesclostridioidesdifficilenamedcontentcolonizationinamurinemodel AT madisonjfitzgerald protonpumpinhibitoromeprazoledoesnotpromotenamedcontentcontenttypegenusspeciesclostridioidesdifficilenamedcontentcolonizationinamurinemodel AT patrickdschloss protonpumpinhibitoromeprazoledoesnotpromotenamedcontentcontenttypegenusspeciesclostridioidesdifficilenamedcontentcolonizationinamurinemodel
_version_	1718428015237529600

The Proton Pump Inhibitor Omeprazole Does Not Promote <named-content content-type="genus-species">Clostridioides difficile</named-content> Colonization in a Murine Model

Ejemplares similares