{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:47:47Z","timestamp":1787028467740,"version":"build-2736575974"},"reference-count":28,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2021,12,19]],"date-time":"2021-12-19T00:00:00Z","timestamp":1639872000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Biocodex (France)","award":["BMF Belux 2018"],"award-info":[{"award-number":["BMF Belux 2018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Proton pump inhibitors (PPI) may improve symptoms in functional dyspepsia (FD) through duodenal eosinophil-reducing effects. However, the contribution of the microbiome to FD symptoms and its interaction with PPI remains elusive. Aseptic duodenal brushings and biopsies were performed before and after PPI intake (4 weeks Pantoprazole 40 mg daily, FD-starters and controls) or withdrawal (2 months, FD-stoppers) for 16S-rRNA sequencing. Between- and within-group changes in genera or diversity and associations with symptoms or duodenal factors were analyzed. In total, 30 controls, 28 FD-starters and 19 FD-stoppers were followed. Mucus-associated Porphyromonas was lower in FD-starters vs. controls and correlated with symptoms in FD and duodenal eosinophils in both groups, while Streptococcus correlated with eosinophils in controls. Although clinical and eosinophil-reducing effects of PPI therapy were unrelated to microbiota changes in FD-starters, increased Streptococcus was associated with duodenal PPI effects in controls and remained higher despite withdrawal of long-term PPI therapy in FD-stoppers. Thus, duodenal microbiome analysis demonstrated differential mucus-associated genera, with a potential role of Porphyromonas in FD pathophysiology. While beneficial effects of short-term PPI therapy were not associated with microbial changes in FD-starters, increased Streptococcus and its association with PPIeffects in controls suggest a role for duodenal dysbiosis after long-term PPI therapy.<\/jats:p>","DOI":"10.3390\/ijms222413609","type":"journal-article","created":{"date-parts":[[2021,12,19]],"date-time":"2021-12-19T20:37:27Z","timestamp":1639946247000},"page":"13609","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Duodenal Dysbiosis and Relation to the Efficacy of Proton Pump Inhibitors in Functional Dyspepsia"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3195-4996","authenticated-orcid":false,"given":"Lucas","family":"Wauters","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Hospitals Leuven, 3000 Leuven, Belgium"},{"name":"Translational Research in Gastrointestinal Disorders (TARGID), KU Leuven, 3000 Leuven, Belgium"},{"name":"VIB Center for Microbiology, 3000 Leuven, Belgium"},{"name":"Department of Microbiology and Immunology, Rega Institute, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9660-7621","authenticated-orcid":false,"given":"Ra\u00fal Y.","family":"Tito","sequence":"additional","affiliation":[{"name":"VIB Center for Microbiology, 3000 Leuven, Belgium"},{"name":"Department of Microbiology and Immunology, Rega Institute, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Ceulemans","sequence":"additional","affiliation":[{"name":"Translational Research in Gastrointestinal Disorders (TARGID), KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten","family":"Lambaerts","sequence":"additional","affiliation":[{"name":"Translational Research in Gastrointestinal Disorders (TARGID), KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Accarie","sequence":"additional","affiliation":[{"name":"Translational Research in Gastrointestinal Disorders (TARGID), KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leen","family":"Rymenans","sequence":"additional","affiliation":[{"name":"VIB Center for Microbiology, 3000 Leuven, Belgium"},{"name":"Department of Microbiology and Immunology, Rega Institute, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chlo\u00eb","family":"Verspecht","sequence":"additional","affiliation":[{"name":"VIB Center for Microbiology, 3000 Leuven, Belgium"},{"name":"Department of Microbiology and Immunology, Rega Institute, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joran","family":"Toth","sequence":"additional","affiliation":[{"name":"Translational Research in Gastrointestinal Disorders (TARGID), KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0886-1123","authenticated-orcid":false,"given":"Raf","family":"Mols","sequence":"additional","affiliation":[{"name":"Drug Delivery and Disposition, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2595-388X","authenticated-orcid":false,"given":"Patrick","family":"Augustijns","sequence":"additional","affiliation":[{"name":"Drug Delivery and Disposition, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Tack","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Hospitals Leuven, 3000 Leuven, Belgium"},{"name":"Translational Research in Gastrointestinal Disorders (TARGID), KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Vanuytsel","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Hospitals Leuven, 3000 Leuven, Belgium"},{"name":"Translational Research in Gastrointestinal Disorders (TARGID), KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen","family":"Raes","sequence":"additional","affiliation":[{"name":"VIB Center for Microbiology, 3000 Leuven, Belgium"},{"name":"Department of Microbiology and Immunology, Rega Institute, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1053\/j.gastro.2016.02.011","article-title":"Gastroduodenal Disorders","volume":"150","author":"Stanghellini","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1136\/gutjnl-2019-318536","article-title":"Novel concepts in the pathophysiology and treatment of functional dyspepsia","volume":"69","author":"Wauters","year":"2020","journal-title":"Gut"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"41","DOI":"10.14309\/ajg.0000000000000485","article-title":"What Causes Functional Gastrointestinal Disorders? A Proposed Disease Model","volume":"115","author":"Talley","year":"2020","journal-title":"Am. J. Gastroenterol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.cgh.2018.08.054","article-title":"The Gut Microbiome in Adult and Pediatric Functional Gastrointestinal Disorders","volume":"17","author":"Shin","year":"2019","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1007\/s11894-017-0577-6","article-title":"The Gastric and Intestinal Microbiome: Role of Proton Pump Inhibitors","volume":"19","author":"Minalyan","year":"2017","journal-title":"Curr. Gastroenterol. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/nrmicro3552","article-title":"Gut biogeography of the bacterial microbiota","volume":"14","author":"Donaldson","year":"2016","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1053\/j.gastro.2020.04.014","article-title":"Worldwide Prevalence and Burden of Functional Gastrointestinal Disorders, Results of Rome Foundation Global Study","volume":"160","author":"Sperber","year":"2021","journal-title":"Gastroenterology"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Sundin, O.H., Mendoza-Ladd, A., Zeng, M., Diaz-Ar\u00e9valo, D., Morales, E., Fagan, B.M., Ordo\u00f1ez, J., Velez, P., Antony, N., and McCallum, R.W. (2017). The human jejunum has an endogenous microbiota that differs from those in the oral cavity and colon. BMC Microbiol., 17.","DOI":"10.1186\/s12866-017-1059-6"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1111\/apt.13622","article-title":"Characterisation of the gastrointestinal mucosa-associated microbiota: A novel technique to prevent cross-contamination during endoscopic procedures","volume":"43","author":"Shanahan","year":"2016","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1136\/gutjnl-2016-312574","article-title":"Dyspepsia and the microbiome: Time to focus on the small intestine","volume":"66","author":"Zhong","year":"2017","journal-title":"Gut"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1053\/j.gastro.2015.06.043","article-title":"Proton Pump Inhibitors Alter Specific Taxa in the Human Gastrointestinal Microbiome: A Crossover Trial","volume":"149","author":"Freedberg","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6633","DOI":"10.1128\/AEM.01437-16","article-title":"Effects of Proton Pump Inhibitors on the Gastric Mucosa-Associated Microbiota in Dyspeptic Patients","volume":"82","author":"Palladini","year":"2016","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1053\/j.gastro.2019.05.056","article-title":"Safety of Proton Pump Inhibitors Based on a Large, Multi-Year, Randomized Trial of Patients Receiving Rivaroxaban or Aspirin","volume":"157","author":"Moayyedi","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1038\/ajg.2017.154","article-title":"ACG and CAG Clinical Guideline: Management of Dyspepsia","volume":"112","author":"Moayyedi","year":"2017","journal-title":"Am. J. Gastroenterol."},{"key":"ref_15","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_16","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1159\/000504090","article-title":"Higher Levels of Streptococcus in Upper Gastrointestinal Mucosa Associated with Symptoms in Patients with Functional Dyspepsia","volume":"101","author":"Fukui","year":"2020","journal-title":"Digestion"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2012","DOI":"10.1038\/s41467-019-09964-7","article-title":"Small intestinal microbial dysbiosis underlies symptoms associated with functional gastrointestinal disorders","volume":"10","author":"Saffouri","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1038\/s41598-020-57468-y","article-title":"Evidence of altered mucosa-associated and fecal microbiota composition in patients with Irritable Bowel Syndrome","volume":"10","author":"Sundin","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1016\/j.cgh.2020.05.019","article-title":"Gastrointestinal Eosinophil Responses in a Longitudinal, Randomized Trial of Peanut Oral Immunotherapy","volume":"19","author":"Wright","year":"2021","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3298","DOI":"10.1038\/s41467-019-10914-6","article-title":"Country-wide medical records infer increased allergy risk of gastric acid inhibition","volume":"10","author":"Jordakieva","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1080\/14728222.2020.1752181","article-title":"Duodenal inflammation: An emerging target for functional dyspepsia?","volume":"24","author":"Wauters","year":"2020","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1002\/ueg2.12061","article-title":"United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on functional dyspepsia","volume":"9","author":"Wauters","year":"2021","journal-title":"United Eur. Gastroenterol. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/S2468-1253(18)30003-7","article-title":"Epidemiology, clinical characteristics, and associations for symptom-based Rome IV functional dyspepsia in adults in the USA, Canada, and the UK: A cross-sectional population-based study","volume":"3","author":"Aziz","year":"2018","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1186\/s40168-018-0605-2","article-title":"Simple statistical identification and removal of contaminant sequences in marker-gene and metagenomics data","volume":"6","author":"Davis","year":"2018","journal-title":"Microbiome"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s40168-015-0083-8","article-title":"Deriving accurate microbiota profiles from human samples with low bacterial content through post-sequencing processing of Illumina MiSeq data","volume":"3","author":"Leong","year":"2015","journal-title":"Microbiome"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1002\/art.39802","article-title":"Brief Report: Dialister as a Microbial Marker of Disease Activity in Spondyloarthritis","volume":"69","author":"Tito","year":"2017","journal-title":"Arthritis Rheumatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s40168-017-0267-5","article-title":"Optimizing methods and dodging pitfalls in microbiome research","volume":"5","author":"Kim","year":"2017","journal-title":"Microbiome"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/2049-2618-2-30","article-title":"LotuS: An efficient and user-friendly OTU processing pipeline","volume":"2","author":"Hildebrand","year":"2014","journal-title":"Microbiome"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/24\/13609\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:52:03Z","timestamp":1760169123000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/24\/13609"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,19]]},"references-count":28,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["ijms222413609"],"URL":"https:\/\/doi.org\/10.3390\/ijms222413609","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,19]]}}}