The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
QIIME allows analysis of high-throughput community sequencing data
Caporaso, J. G., Kuczynski, J., Stombaugh, J., Bittinger, K., Bushman, F. D., Costello, E. K., Fierer, N., Peña, A. G., Goodrich, J. K., Gordon, J. I., et al. (2010) · Nature Methods · doi:10.1038/nmeth.f.303 · Cited by 34,887
Search and clustering orders of magnitude faster than BLAST
Edgar, R. C. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq461 · Cited by 21,098
UCHIME improves sensitivity and speed of chimera detection
Edgar, R. C., Haas, B. J., Clemente, J. C., Quince, C., & Knight, R. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr381 · Cited by 15,114
Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences
Langille, M. G. I., Zaneveld, J., Caporaso, J. G., McDonald, D., Knights, D., Reyes, J. A., Clemente, J. C., Burkepile, D. E., Vega Thurber, R. L., Knight, R., et al. (2013) · Nature Biotechnology · doi:10.1038/nbt.2676 · Cited by 9,116
Enterotypes of the human gut microbiome
MetaHIT Consortium (additional members), Arumugam, M., Raes, J., Pelletier, E., Le Paslier, D., Yamada, T., Mende, D. R., Fernandes, G. R., Tap, J., Bruls, T., et al. (2011) · Nature · doi:10.1038/nature09944 · Cited by 7,548
STAMP: statistical analysis of taxonomic and functional profiles
Parks, D. H., Tyson, G. W., Hugenholtz, P., & Beiko, R. G. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu494 · Cited by 4,246
The Human Intestinal Microbiome in Health and Disease
Lynch, S. V., & Pedersen, O. (2016) · New England Journal of Medicine · doi:10.1056/nejmra1600266 · Cited by 3,637
Data, information, knowledge and principle: back to metabolism in KEGG
Kanehisa, M. I., Goto, S., Sato, Y., Kawashima, M., Furumichi, M., & Tanabe, M. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt1076 · Cited by 3,103
Machiels, K., Joossens, M., Sabino, J., De Preter, V., Arijs, I., Eeckhaut, V., Ballet, V., Claes, K., Van Immerseel, F., Verbeke, K., et al. (2014) · Gut · doi:10.1136/gutjnl-2013-304833 · Cited by 1,904
Proton pump inhibitors affect the gut microbiome
Imhann, F., Bonder, M. J., Vich Vila, A., Fu, J., Mujagic, Z., Vork, L., Tigchelaar, E. F., Jankipersadsing, S. A., Cenit, M. C., Harmsen, H. J. M., et al. (2016) · Gut · doi:10.1136/gutjnl-2015-310376 · Cited by 1,371 · cited 2×
“(4,17) In our results, as shown in Fig.”
Flagged first, then by citations
Cited by
Sorted by citations
Items 101–121 of 121
Analysis of Gut Microbiota and Their Metabolites in CADASIL Patients
Watanabe-Hosomi, A., Inoüe, R., Mizuta, I., Matsuura, J., Matsuura, H., Fukunaga, D., Ohara, T., Naito, Y., & Mizuno, T. (2025) · Journal of Clinical Neurology · doi:10.3988/jcn.2025.0231 · Cited by 2
Self-citationThe Gastric Microbiome in Benign and Malignant Diseases
Bartelli, T. F., Coelho, L. G. V., & Dias‐Neto, E. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-815249-2.00010-5 · Cited by 2
Drall, K. M., Tun, H. M., & Kozyrskyj, A. L. (2018) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2018.00430 · Cited by 2
Periodontitis and Inflammatory Bowel Diseases: Mechanistic Evidence
Colombo, A. P. V., de Oliveira, A. M., Kamada, N., & Kitamoto, S. (2026) · Journal of Periodontal Research · doi:10.1111/jre.70124 · Cited by 1
ASSESSMENT OF THE INTESTINAL MICROBIOTA IN ADULTS WITH EROSIVE ESOPHAGITIS
Baima, D. C., Carvalho, N. S., Barbuti, R. C., & Navarro-Rodríguez, T. (2021) · Arquivos de Gastroenterologia · doi:10.1590/s0004-2803.202100000-29 · Cited by 1
Tanimaru, A. N., Mendes, A. B., de Mello, D. S. F., Mendes, F. G., & Carvalho, C. D. F. (2024) · Revista de Medicina · doi:10.11606/issn.1679-9836.v103i3e-210046 · Cited by 1
Helicobacter pylori Eradication after Endoscopic Resection of Gastric Epithelial Neoplasms
Choi, J. M., & Kim, S. G. (2019) · The Korean Journal of Helicobacter and Upper Gastrointestinal Research · doi:10.7704/kjhugr.2019.0020 · Cited by 1
Acid suppression and effects on the gastrointestinal microbiome
Korus, H., & Vakil, N. B. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-95070-1.00011-4 · Cited by 1
Baima, D. C. (2020) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.5.2020.tde-01072021-115140
Microbial Drug Interactions and Human Health
Ilhan, Z. E., & Herbst‐Kralovetz, M. M. (2022) · Royal Society of Chemistry eBooks · doi:10.1039/9781839160950-00120
Saka, Y., Naruse, T., Chikamatsu, T., Mitani, K., Hayashi, M., Matsumoto, J., Yosizawa, Y., Mimura, T., Takahashi, H., & Watanabe, Y. (2023) · The Nephron journals/Nephron journals · doi:10.1159/000531028
Proton pump inhibitors and stomach neoplasm
Guo, J., & Zhou, Z. (2020) · Oncology and Translational Medicine · doi:10.1007/s10330-019-0384-4
Kalra, S., Joshi, A. S., TIWASKAR, M. H., Agrawal, N. K., Shaikh, S. S., Bhatia, B. S., Jhingan, A. K., Rawal, P., Das, A. K., Nishad, S. K., et al. (2023) · Journal of the Association of Physicians of India · doi:10.59556/japi.71.0409
Saifon, W., Sensorn, I., Trachu, N., Oranratnachai, S., Charoenyingwattana, A., Runcharoen, C., Monnamo, N., Sukkasem, W., Inchareon, P., Suwatanapongched, T., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21069425
Zhang, J., Zhang, C., Zhang, Q., Yu, L., Chen, W., Xue, Y., & Zhai, Q. (2023) · Figshare · doi:10.6084/m9.figshare.23542924
Mlčůchová, N., Böhm, J., Kunovský, L., Haruštiak, T., Boleij, A., Linhartová, P. B., & The Czech GERD Collaborative Group (2025) · Research Square · doi:10.21203/rs.3.rs-8385155/v1
Dinesh, D., Morgan, X. C., Kim, H., Scott, T. M., Garelnabi, M., Lee, J. S., Mangano, K. M., Nguyen, L. H., Huttenhower, C., Tucker, K. L., et al. (2025) · Pharmacology Research & Perspectives · doi:10.1002/prp2.70205
Impact of proton pump inhibitor use on microbiota and diversity
Alsharef, A. S., Alsaedi, E. A. H., Almohmmadi, G. T., Alahmadi, K., Alhemshy, L. Z., Albugami, M. K., Alghanim, W. S., Alharbi, S. S., Alahmadi, Y. K., Aljohani, Y. S., et al. (2025) · International Journal of Community Medicine and Public Health · doi:10.18203/2394-6040.ijcmph20254453
Sato, S., Chinda, D., Mikami, K., Tobinai, M., Ishidoya, N., Furusawa, K., Miyashiro, K., Yoshida, K., Iino, C., Sawada, K., et al. (2026) · Digestion · doi:10.1159/000552238
El-Tahir, R., Qureshi, S., Ashfaq, N., Sikandar, S., Omar, S., Shah, P., & Bitar, E. (2026) · Open Journal of Internal Medicine · doi:10.4236/ojim.2026.163028
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
