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The influence of long-term use of proton pump inhibitors on the gut microbiota: an age-sex-matched case-control study
Open accessAbstract
Proton pump inhibitors (PPIs) are widely used to treat gastro-esophageal reflux and prevent gastric ulcers, and have been considered as low risk. However, recent studies have identified possible associations between PPI use and gut microbiota, suggesting that PPIs use increases the risk of enteric infections, including Clostridium difficile infection. To investigate gut microbiota in Japanese PPIs users, we conducted 16S metagenomics analysis of fecal samples collected from PPI users and healthy adults. In total, 36 PPI users and 36 PPI non-users (as control subjects) matched by age and sex were recruited and fecal samples were obtained to analyze the gut microbiome using 16S rRNA gene sequencing. There were significant differences in the microbial structure between PPI non-users and PPI users. In contrast, the analysis of α-diversity revealed no significant differences between PPI non-users and PPI users. When comparing in genus level between these two groups, the genera Streptococcus was significantly abundant and the genera Faecalibacterium was significantly decreased in PPI users. Our findings indicate a probable association between PPI use and the alternation of microbiota. These alterations might provide a mechanism by which PPIs predispose enteric infection such as Clostridium difficile infection.
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![Fig. 2 The α-diversity indices between PPI non-users and PPI users. We compared α-diversity indices [the observed species and the Chao 1 index (OTU richness estimation), and the Shannon index (OTU evenness estimation)] using Student’s unpaired t tests.](/paper-figures/e98a17577aa7481280002fa4182a3879/the-influence-of-long-term-use-of-proton-pump-inhibitors-on-the-gut-microbiota-figure-2.jpg)
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“likely due to PPI-driven gastric hypo-chlorhydria, which can cause also significant changes in gut microbiota composition[9-11]”
From Proton pump inhibitors and dysbiosis: current knowledge and aspects to be clarified (2019) · cites this paper as [11]
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Metadata
- Authors
- Takagi, T., Naito, Y., Inoue, R., Kashiwagi, S., Uchiyama, K., Mizushima, K., Tsuchiya, S., Okayama, T., Dohi, O., Yoshida, N., Kamada, K., Ishikawa, T., Handa, O., Konishi, H., Okuda, K., Tsujimoto, Y., Ohnogi, H., & Itoh, Y.
- Affiliations
- Kyoto Prefectural University of Medicine (JP)
- Laboratory of Animal Science, Kyoto Prefectural University
- Takara BIO Inc. (Japan) (JP)
- Corresponding author
- Takagi, Tomohisa
- ORCID
- Venue
- Journal of Clinical Biochemistry and Nutrition
- Published
- 2018
- Volume
- 62
- Issue
- 1
- Pages
- 100-105
- ISSN
- 0912-0009 (ISSN-L)
- 1880-5086
- PMC
- PMC5773837
- OpenAlex
- W2771725285
- Cited by
- 121
- References
- 23
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 9 · 2023: 11 · 2022: 20 · 2021: 9 · 2020: 20 · 2019: 22 · 2018: 15
- FWCI
- 6.37
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Journal of Clinical Biochemistry and Nutrition (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Agriculture and Food Research Organization
- Japan Society for the Promotion of Science (16K09322, 16H05289)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Medicine › Infectious Diseases › Clostridium difficile and Clostridium perfringens research
- Keywords
- proton pump inhibitors, gut microbiota, Clostridium difficile infection, gastrointestinal infections, Faecalibacterium, Streptococcus, microbial diversity, fecal microbiota, long-term drug use, Japanese adults
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