{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:52:55Z","timestamp":1787028775710,"version":"build-2736575974"},"reference-count":49,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,9,27]],"date-time":"2022-09-27T00:00:00Z","timestamp":1664236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"INHA UNIVERSITY Research Grant","award":["no. NRF-2022R1F1A1067621"],"award-info":[{"award-number":["no. NRF-2022R1F1A1067621"]}]},{"name":"National Research Foundation of Korea (NRF)","award":["no. NRF-2022R1F1A1067621"],"award-info":[{"award-number":["no. NRF-2022R1F1A1067621"]}]},{"name":"Ministry of Science, ICT &amp; Future Planning","award":["no. NRF-2022R1F1A1067621"],"award-info":[{"award-number":["no. NRF-2022R1F1A1067621"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>The gut microbiota are regarded as a functional organ that plays a substantial role in human health and disease. Proton pump inhibitors (PPIs) are widely used in medicine but can induce changes in the overall gut microbiome and cause disease-associated dysbiosis. The microbiome of the duodenum has not been sufficiently studied, and the effects of PPIs on the duodenal microbiome are poorly understood. In this study, we investigated the effect of PPI administration on duodenum microbiota in patients with a gastric ulcer. A total of 12 gastric ulcer patients were included, and PPI (Ilaprazole, Noltec\u00ae, 10 mg) was prescribed in all patients for 4 weeks. A total of 17 samples from the second portion of the duodenum were analyzed. Microbiome compositions were assessed by sequencing the V3\u2013V4 region of the 16s rRNA gene (Miseq). Changes in microbiota compositions after 4 weeks of PPI treatment were analyzed. a-Diversity was higher after PPI treatment (p = 0.02, at Chao1 index), and \u03b2-diversity was significantly different after treatment (p = 0.007). Welch\u2019s t-test was used to investigate changes in phyla, genus, and species level, and the abundance of Akkermansia muciniphila, belonging to the phylum Verrucomicrobia, and Porphyromonas endodontalis, belonging to the phylum Bacteroidetes, was significantly increased after treatment (p = 0.044 and 0.05). PPI administration appears to induce duodenal microbiome dysbiosis while healing gastric ulcers. Further large-scale studies on the effects of PPIs on the duodenal microbiome are required.<\/jats:p>","DOI":"10.3390\/life12101505","type":"journal-article","created":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T01:51:49Z","timestamp":1664329909000},"page":"1505","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Effect of a Proton Pump Inhibitor on the Duodenum Microbiome of Gastric Ulcer Patients"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3596-9420","authenticated-orcid":false,"given":"Jung-Hyun","family":"Lim","sequence":"first","affiliation":[{"name":"Digestive Disease Center, Department of Internal Medicine, Inha University School of Medicine, Incheon 22332, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jongbeom","family":"Shin","sequence":"additional","affiliation":[{"name":"Digestive Disease Center, Department of Internal Medicine, Inha University School of Medicine, Incheon 22332, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Seok","family":"Park","sequence":"additional","affiliation":[{"name":"Digestive Disease Center, Department of Internal Medicine, Inha University School of Medicine, Incheon 22332, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1046\/j.1365-2036.2001.00904.x","article-title":"Meta-analysis of randomized controlled trials comparing standard clinical doses of omeprazole and lansoprazole in erosive oesophagitis","volume":"15","author":"Sharma","year":"2001","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1111\/j.1365-2036.2005.02391.x","article-title":"Meta-analysis: Proton-pump inhibition in high-risk patients with acute peptic ulcer bleeding","volume":"21","author":"Bardou","year":"2005","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1111\/j.1572-0241.1999.1123_a.x","article-title":"Updated guidelines for the diagnosis and treatment of gastroesophageal reflux disease. The Practice Parameters Committee of the American College of Gastroenterology","volume":"94","author":"DeVault","year":"1999","journal-title":"Am. J. Gastroenterol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1177\/1756283X11398735","article-title":"Proton-pump inhibitors for the treatment of functional dyspepsia","volume":"4","author":"Suzuki","year":"2011","journal-title":"Ther. Adv. Gastroenterol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/290159a0","article-title":"Substituted benzimidazoles inhibit gastric acid secretion by blocking (H+ + K+)ATPase","volume":"290","author":"Fellenius","year":"1981","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"25","DOI":"10.5056\/jnm.2013.19.1.25","article-title":"Pharmacokinetics and pharmacodynamics of the proton pump inhibitors","volume":"19","author":"Shin","year":"2013","journal-title":"J. Neurogastroenterol. Motil."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/s00535-021-01769-0","article-title":"Evidence-based clinical practice guidelines for peptic ulcer disease 2020","volume":"56","author":"Kamada","year":"2021","journal-title":"J. Gastroenterol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/ajg.2011.480","article-title":"Management of patients with ulcer bleeding","volume":"107","author":"Laine","year":"2012","journal-title":"Am. J. Gastroenterol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1016\/S0140-6736(15)00276-7","article-title":"Perforated peptic ulcer","volume":"386","author":"Thorsen","year":"2015","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"552102","DOI":"10.3389\/fphar.2020.552102","article-title":"Use of Proton Pump Inhibitors in Hungary: Mixed-Method Study to Reveal Scale and Characteristics","volume":"11","author":"Matuz","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e00037","DOI":"10.1128\/mBio.00037-15","article-title":"Analysis of the upper respiratory tract microbiotas as the source of the lung and gastric microbiotas in healthy individuals","volume":"6","author":"Bassis","year":"2015","journal-title":"mBio"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1073\/pnas.0506655103","article-title":"Molecular analysis of the bacterial microbiota in the human stomach","volume":"103","author":"Bik","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4202","DOI":"10.1038\/srep04202","article-title":"Stomach microbiota composition varies between patients with non-atrophic gastritis and patients with intestinal type of gastric cancer","volume":"4","author":"Mantilla","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"610421","DOI":"10.1155\/2014\/610421","article-title":"Culturable bacterial microbiota of the stomach of Helicobacter pylori positive and negative gastric disease patients","volume":"2014","author":"Khosravi","year":"2014","journal-title":"Sci. World J."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Li, X.X., Wong, G.L., To, K.F., Wong, V.W., Lai, L.H., Chow, D.K., Lau, J.Y., Sung, J.J., and Ding, C. (2009). Bacterial microbiota profiling in gastritis without Helicobacter pylori infection or non-steroidal anti-inflammatory drug use. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0007985"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1136\/gutjnl-2021-325097","article-title":"Proton pump inhibitors and risk of gastric cancer: Population-based cohort study","volume":"71","author":"Abrahami","year":"2022","journal-title":"Gut"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"84","DOI":"10.2174\/138920009787048392","article-title":"The effect of proton pump inhibitors on the human microbiota","volume":"10","author":"Vesper","year":"2009","journal-title":"Curr. Drug Metab."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1046\/j.1365-2036.2001.00888.x","article-title":"Non-Helicobacter pylori bacterial flora during acid-suppressive therapy: Differential findings in gastric juice and gastric mucosa","volume":"15","author":"Sanduleanu","year":"2001","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1002\/hep.30304","article-title":"Proton Pump Inhibitors Are Associated With Minimal and Overt Hepatic Encephalopathy and Increased Mortality in Patients With Cirrhosis","volume":"70","author":"Nardelli","year":"2019","journal-title":"Hepatology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1177\/2050640618773564","article-title":"Association of proton pump inhibitors with the risk of hepatic encephalopathy during hospitalization for liver cirrhosis","volume":"6","author":"Zhu","year":"2018","journal-title":"United Eur. Gastroenterol. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1002\/hep.28737","article-title":"Proton pump inhibitors as a risk factor for hepatic encephalopathy and spontaneous bacterial peritonitis in patients with cirrhosis with ascites","volume":"64","author":"Dam","year":"2016","journal-title":"Hepatology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"6817","DOI":"10.3748\/wjg.v21.i22.6817","article-title":"What are the effects of proton pump inhibitors on the small intestine?","volume":"21","author":"Fujimori","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.cgh.2012.12.011","article-title":"Proton pump inhibitor use and the risk of small intestinal bacterial overgrowth: A meta-analysis","volume":"11","author":"Lo","year":"2013","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1053\/j.gastro.2018.02.010","article-title":"The Duodenum harbors a Broad Untapped Therapeutic Potential","volume":"154","author":"Nieuwdorp","year":"2018","journal-title":"Gastroenterology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.giec.2016.08.001","article-title":"Anatomy and Physiology of the Small Bowel","volume":"27","author":"Volk","year":"2017","journal-title":"Gastrointest. Endosc. Clin. N. Am."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/s41579-020-0433-9","article-title":"Gut microbiota in human metabolic health and disease","volume":"19","author":"Fan","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1053\/j.gastro.2020.12.016","article-title":"Proton Pump Inhibitors Reduce Duodenal Eosinophilia, Mast Cells, and Permeability in Patients With Functional Dyspepsia","volume":"160","author":"Wauters","year":"2021","journal-title":"Gastroenterology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"364","DOI":"10.5946\/ce.2015.48.5.364","article-title":"Clinical Practice Guidelines for Endoscope Reprocessing","volume":"48","author":"Oh","year":"2015","journal-title":"Clin. Endosc."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1007\/BF01312726","article-title":"Correlation of gastric ulcer healing features by endoscopy, stereoscopic microscopy, and histology, and a reclassification of the epithelial regenerative process","volume":"25","author":"Miyake","year":"1980","journal-title":"Dig. Dis. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2440","DOI":"10.1016\/S0021-9258(17)41965-X","article-title":"Molecular cloning of human intestinal mucin (MUC2) cDNA. Identification of the amino terminus and overall sequence similarity to prepro-von Willebrand factor","volume":"269","author":"Gum","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1038\/nrgastro.2012.161","article-title":"The importance of the gut microbiota after bariatric surgery","volume":"9","author":"Clement","year":"2012","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1097\/MOG.0b013e328341dc67","article-title":"Small intestine and microbiota","volume":"27","author":"Cotter","year":"2011","journal-title":"Curr. Opin. Gastroenterol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Mailhe, M., Ricaboni, D., Vitton, V., Gonzalez, J.M., Bachar, D., Dubourg, G., Cadoret, F., Robert, C., Delerce, J., and Levasseur, A. (2018). Repertoire of the gut microbiota from stomach to colon using culturomics and next-generation sequencing. BMC Microbiol., 18.","DOI":"10.1186\/s12866-018-1304-7"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e00126-19","DOI":"10.1128\/mSphere.00126-19","article-title":"Spatial and Temporal Analysis of the Stomach and Small-Intestinal Microbiota in Fasted Healthy Humans","volume":"4","author":"Seekatz","year":"2019","journal-title":"mSphere"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"906","DOI":"10.3389\/fimmu.2020.00906","article-title":"The Genus Alistipes: Gut Bacteria With Emerging Implications to Inflammation, Cancer, and Mental Health","volume":"11","author":"Parker","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"157","DOI":"10.2217\/fmb-2016-0130","article-title":"Roseburia spp.: A marker of health?","volume":"12","author":"Smida","year":"2017","journal-title":"Future Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"10123","DOI":"10.3402\/jom.v4i0.10123","article-title":"Porphyromonas endodontalis in chronic periodontitis: A clinical and microbiological cross-sectional study","volume":"4","author":"Marcantonio","year":"2012","journal-title":"J. Oral Microbiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1177\/154405910608500407","article-title":"Subgingival and tongue microbiota during early periodontitis","volume":"85","author":"Tanner","year":"2006","journal-title":"J. Dent. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/s41575-022-00631-9","article-title":"Akkermansia muciniphila: Paradigm for next-generation beneficial microorganisms","volume":"19","author":"Cani","year":"2022","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"van Passel, M.W., Kant, R., Zoetendal, E.G., Plugge, C.M., Derrien, M., Malfatti, S.A., Chain, P.S., Woyke, T., Palva, A., and de Vos, W.M. (2011). The genome of Akkermansia muciniphila, a dedicated intestinal mucin degrader, and its use in exploring intestinal metagenomes. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0016876"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"166","DOI":"10.3389\/fmicb.2011.00166","article-title":"Modulation of Mucosal Immune Response, Tolerance, and Proliferation in Mice Colonized by the Mucin-Degrader Akkermansia muciniphila","volume":"2","author":"Derrien","year":"2011","journal-title":"Front. Microbiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1136\/gut.2009.191320","article-title":"Acute appendicitis is characterised by local invasion with Fusobacterium nucleatum\/necrophorum","volume":"60","author":"Swidsinski","year":"2011","journal-title":"Gut"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2420","DOI":"10.1038\/ajg.2010.281","article-title":"Mucolytic bacteria with increased prevalence in IBD mucosa augment in vitro utilization of mucin by other bacteria","volume":"105","author":"Png","year":"2010","journal-title":"Am. J. Gastroenterol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"8292","DOI":"10.1038\/ncomms9292","article-title":"The outer mucus layer hosts a distinct intestinal microbial niche","volume":"6","author":"Li","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Tarnawski, A.S., and Ahluwalia, A. (2021). The Critical Role of Growth Factors in Gastric Ulcer Healing: The Cellular and Molecular Mechanisms and Potential Clinical Implications. Cells, 10.","DOI":"10.3390\/cells10081964"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e13841","DOI":"10.1111\/nmo.13841","article-title":"Proton pump inhibitors enhance intestinal permeability via dysbiosis of gut microbiota under stressed conditions in mice","volume":"32","author":"Takashima","year":"2020","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"12015","DOI":"10.1038\/ncomms12015","article-title":"Alterations of the human gut microbiome in multiple sclerosis","volume":"7","author":"Jangi","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"20063","DOI":"10.1038\/s41598-020-77245-1","article-title":"The impacts of acid suppression on duodenal microbiota during the early phase of severe acute pancreatitis","volume":"10","author":"Ma","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"E291","DOI":"10.1055\/s-0043-102936","article-title":"Proton pump inhibitor is a risk factor for recurrence of common bile duct stones after endoscopic sphincterotomy\u2014propensity score matching analysis","volume":"5","author":"Fukuba","year":"2017","journal-title":"Endosc. Int. Open"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/12\/10\/1505\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:40:19Z","timestamp":1760143219000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/12\/10\/1505"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,27]]},"references-count":49,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["life12101505"],"URL":"https:\/\/doi.org\/10.3390\/life12101505","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,27]]}}}