PMID- 31748246
OWN - NLM
STAT- MEDLINE
DCOM- 20200605
LR  - 20201209
IS  - 2379-5042 (Electronic)
IS  - 2379-5042 (Linking)
VI  - 4
IP  - 6
DP  - 2019 Nov 20
TI  - The Proton Pump Inhibitor Omeprazole Does Not Promote Clostridioides difficile 
      Colonization in a Murine Model.
LID - 10.1128/mSphere.00693-19 [doi]
LID - e00693-19
AB  - 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.
CI  - Copyright (c) 2019 Tomkovich et al.
FAU - Tomkovich, Sarah
AU  - Tomkovich S
AD  - Department of Microbiology and Immunology, University of Michigan, Ann Arbor, 
      Michigan, USA.
FAU - Lesniak, Nicholas A
AU  - Lesniak NA
AD  - Department of Microbiology and Immunology, University of Michigan, Ann Arbor, 
      Michigan, USA.
FAU - Li, Yuan
AU  - Li Y
AD  - Department of Microbiology and Immunology, University of Michigan, Ann Arbor, 
      Michigan, USA.
FAU - Bishop, Lucas
AU  - Bishop L
AD  - Department of Microbiology and Immunology, University of Michigan, Ann Arbor, 
      Michigan, USA.
FAU - Fitzgerald, Madison J
AU  - Fitzgerald MJ
AD  - Department of Microbiology and Immunology, University of Michigan, Ann Arbor, 
      Michigan, USA.
FAU - Schloss, Patrick D
AU  - Schloss PD
AUID- ORCID: 0000-0002-6935-4275
AD  - Department of Microbiology and Immunology, University of Michigan, Ann Arbor, 
      Michigan, USA pschloss@umich.edu.
LA  - eng
GR  - U01 AI124255/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20191120
PL  - United States
TA  - mSphere
JT  - mSphere
JID - 101674533
RN  - 0 (DNA, Bacterial)
RN  - 0 (DNA, Ribosomal)
RN  - 0 (Proton Pump Inhibitors)
RN  - 0 (RNA, Ribosomal, 16S)
RN  - KG60484QX9 (Omeprazole)
SB  - IM
MH  - Animals
MH  - Carrier State/*immunology
MH  - Clostridioides difficile/*growth & development
MH  - Clostridium Infections/*immunology
MH  - Cluster Analysis
MH  - DNA, Bacterial/chemistry/genetics
MH  - DNA, Ribosomal/chemistry/genetics
MH  - Disease Models, Animal
MH  - *Disease Susceptibility
MH  - Feces/microbiology
MH  - Mice
MH  - Microbiota/drug effects
MH  - Omeprazole/administration & dosage/*adverse effects
MH  - Phylogeny
MH  - Proton Pump Inhibitors/administration & dosage/*adverse effects
MH  - RNA, Ribosomal, 16S/genetics
MH  - Sequence Analysis, DNA
PMC - PMC6887860
OTO - NOTNLM
OT  - 16S rRNA gene
OT  - Clostridioides difficile
OT  - Clostridium difficile
OT  - colonization resistance
OT  - infection
OT  - microbial ecology
OT  - microbiome
OT  - mouse model
OT  - pathogenesis
EDAT- 2019/11/22 06:00
MHDA- 2020/06/06 06:00
PMCR- 2019/11/20
CRDT- 2019/11/22 06:00
PHST- 2019/11/22 06:00 [entrez]
PHST- 2019/11/22 06:00 [pubmed]
PHST- 2020/06/06 06:00 [medline]
PHST- 2019/11/20 00:00 [pmc-release]
AID - 4/6/e00693-19 [pii]
AID - mSphere00693-19 [pii]
AID - 10.1128/mSphere.00693-19 [doi]
PST - epublish
SO  - mSphere. 2019 Nov 20;4(6):e00693-19. doi: 10.1128/mSphere.00693-19.