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Incidence of Small Intestinal Bacterial Overgrowth and Symptoms After 7 Days of Proton Pump Inhibitor Use: A Study on Healthy Volunteers

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Proton pump inhibitors (PPIs) are commonly prescribed drugs. Chronic PPI use has recently been associated with the risk for developing small intestinal bacterial overgrowth (SIBO). It is not known whether the short-term prescription of a PPI can trigger SIBO. Therefore, the aim of the present study was to evaluate the incidence of SIBO and gastrointestinal symptoms after 7 days of PPI use.

Materials and Methods

A prospective, pilot, open-label study was conducted on asymptomatic healthy volunteers. The incidence of SIBO was evaluated at the baseline and after administration of 40 mg of pantoprazole once a day for 7 days, through a glucose breath test. In addition, the presence of gastrointestinal symptoms, the number of bowel movements, and the consistency of stools, according to the Bristol scale, were assessed.


Thirty-eight healthy subjects (71.1% women, mean age 25.18 ± 6.5 years) were analyzed. The incidence of SIBO after 7 days of PPI administration was 7.8% (95% CI 1.6–21.3%). The patients that developed SIBO had a greater prevalence of bloating (p = 0.0002) and flatulence (p = 0.004) after 7 days of treatment.


Our study showed that a short-term 7-day PPI course produced SIBO in 7.8% of healthy subjects. Although, inappropriate use of PPIs should be discouraged, but since more than 90% of subjects who received PPIs for one week did not develop SIBO, the advantages of PPI administration seem to outweigh the disadvantages.

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  1. Schnoll-Sussman F, Niec R, Katz P. Proton pump inhibitors. The good, bad, and ugly. Gastrointest Endosc Clin N Am. 2020;30239–251.

  2. Kahrilas PJ, Shaheen NJ, Vaezi MF et al. American Gastroenterological Association Medical Position Statement on the management of gastroesophageal reflux disease. Gastroenterology 2008;135:1383–1391.

    Article  PubMed  Google Scholar 

  3. Huerta-Iga F, Bielsa-Fernández MV, Remes-Troche JM, Valdovinos-Díaz MA, Tamayo-de la Cuesta JL; en representación del Grupo para el estudio de la ERGE 2015. Diagnosis and treatment of gastroesophageal reflux disease: recommendations of the Asociación Mexicana de Gastroenterología. Diagnóstico y tratamiento de la enfermedad por reflujo gastroesofágico: recomendaciones de la Asociación Mexicana de Gastroenterología. Rev Gastroenterol Mex. 2016;81:208–222.

  4. Kantor ED, Rehm CD, Haas JS et al. Trends in Prescription Drug Use Among Adults in the United States From 1999–2012. JAMA 2015;314:1818–1831.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Compare D, Pica L, Rocco A et al. Effects of long-term PPI treatment on producing bowel symptoms and SIBO. Eur J Clin Invest. 2011;41:380–386.

    Article  PubMed  Google Scholar 

  6. Vaezi MF, Yang YX, Howden CW. Complications of proton pump inhibitor therapy. Gastroenterology 2017;153:35–48.

    Article  CAS  PubMed  Google Scholar 

  7. Eusebi LH, Rabitti S, Artesiani ML et al. Proton pump inhibitors: Risks of long-term use. J Gastroenterol Hepatol. 2017;32:1295–1302.

    Article  PubMed  Google Scholar 

  8. Freedberg DE, Kim LS, Yang YX. The risks and benefits of long-term use of proton pump inhibitors: expert review and best practice advice from the American Gastroenterological Association. Gastroenterology. 2017;152:706–715.

    Article  CAS  PubMed  Google Scholar 

  9. Pereira SP, Gainsborough N, Dowling RH. Drug-induced hypochlorhydria causes high duodenal bacterial counts in the elderly. Aliment Pharmacol Ther 1998;12:99–104.

    Article  CAS  PubMed  Google Scholar 

  10. Lewis SJ, Franco S, Young G et al. Altered bowel function and duodenal bacterial overgrowth in patients treated with omeprazole. Aliment Pharmacol Ther 1996;10:557–561.

    Article  CAS  PubMed  Google Scholar 

  11. Lo WK, Chan WW. Proton pump inhibitor use and the risk of small intestinal bacterial overgrowth: a meta-analysis. Clin Gastroenterol Hepatol. 2013;11:483–490.

    Article  CAS  PubMed  Google Scholar 

  12. Su T, Lai S, Lee A, He X, Chen S. Meta-analysis: proton pump inhibitors moderately increase the risk of small intestinal bacterial overgrowth. J Gastroenterol. 2017;52:27–36.

    Article  Google Scholar 

  13. Bavishi C, Dupont HL. Systematic review: the use of proton pump inhibitors and increased susceptibility to enteric infection. Aliment Pharmacol Ther 2011;34:1269–1281.

    Article  CAS  PubMed  Google Scholar 

  14. Brophy S, Jones KH, Rahman MA et al. Incidence of Campylobacter and Salmonella infections following first prescription for PPI: a cohort study using routine data. Am J Gastroenterol 2013;108:1094–1100.

    Article  PubMed  Google Scholar 

  15. Hafiz RA, Wong C, Paynter S, David M, Peeters G. The Risk of Community-Acquired Enteric Infection in Proton Pump Inhibitor Therapy: Systematic Review and Meta-analysis. Ann Pharmacother. 2018;52:613–622.

    Article  CAS  PubMed  Google Scholar 

  16. Wu HH, Chen YT, Shih CJ, Lee YT, Kuo SC, Chen TL. Association between recent use of proton pump inhibitors and nontyphoid salmonellosis: a nested case-control study. Clin Infect Dis. 2014;59:1554–1558.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Neal KR, Scott HM, Slack RC, Logan RF. Omeprazole as a risk factor for campylobacter gastroenteritis: case-control study. BMJ 1996;312:414–415.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Zavala-Gonzales MA, Azamar-Jacome AA, Meixueiro-Daza A et al. Validation and diagnostic usefulness of gastroesophageal reflux disease questionnaire in a primary care level in Mexico. J Neurogastroenterol Motil. 2014;20:475–482.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Rentz AM, Kahrilas P, Stanghellini V et al. Development and psychometric evaluation of the patient assessment of upper gastrointestinal symptom severity index (PAGI-SYM) in patients with upper gastrointestinal disorders. Qual Life Res. 2004;13:1737–1749.

    Article  CAS  PubMed  Google Scholar 

  20. Rezaie A, Buresi M, Lembo A et al. Hydrogen and Methane-Based Breath Testing in Gastrointestinal Disorders: The North American Consensus. Am J Gastroenterol. 2017;112:775–784.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Cares K, Al-Ansari N, Macha S et al. Short article: risk of small intestinal bacterial overgrowth with chronic use of proton pump inhibitors in children. Eur J Gastroenterol Hepatol. 2017;29:396–399.

    Article  CAS  PubMed  Google Scholar 

  22. Lombardo L, Foti M, Ruggia O, Chiecchio A. Increased incidence of small intestinal bacterial overgrowth during proton pump inhibitor therapy. Clin Gastroenterol Hepatol. 2010;8:504–508.

    Article  PubMed  Google Scholar 

  23. Malfertheiner P, Kandulski A, Venerito M. Proton-pump inhibitors: understanding the complications and risks. Nat Ret Gastroenterol Hepatol. 2017;14:697–710.

    Article  CAS  Google Scholar 

  24. Singh A, Kirby DF. Proton pump inhibitors: Risks and rewards and emerging consequences to the gut microbiome. Nutr Clin Pract. 2018;33:614–624.

    Article  PubMed  Google Scholar 

  25. Naito Y, Kashiwagi K, Takagi T, Andoh A, Inoue R. Intestinal dysbiosis secondary to proton-pump inhibitor use. Digestion. 2018;97:195–204.

    Article  CAS  PubMed  Google Scholar 

  26. Parkman HP, Urbain JL, Knight LC et al. Effect of gastric acid suppressants on human gastric motility. Gut 1998;42:243–250.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Goddard AF, Spiller RC. The effect of omeprazole on gastric juice viscosity, pH, and bacterial counts. Aliment Pharmacol Ther 1996;10:105–109.

    Article  CAS  PubMed  Google Scholar 

  28. Sieczkowska A, Landowski P, Gibas A, Kamińska B, Lifschitz C. Long-term proton pump inhibitor therapy leads to small bowel bacterial overgrowth as determined by breath hydrogen and methane excretion. J. Breath Res. 2018;12:036006.

    Article  CAS  PubMed  Google Scholar 

  29. Freeman R, Dabrera G, Lane C et al. Association between use of proton pump inhibitors and non-typhoidal salmonellosis identified following investigation into an outbreak of Salmonella mikawasima in the UK, 2013. Epidemiol Infect. 2016;144:968–975.

    Article  CAS  PubMed  Google Scholar 

  30. Garcia Rodriguez LA, Ruigomez A, Panes J. Use of acid-sup- pressing drugs and the risk of bacterial gastroenteritis. Clin Gastroenterol Hepatol. 2007;5:1418–1423.

    Article  PubMed  Google Scholar 

  31. Pimentel M. Evaluating a bacterial hypothesis in IBS using a modification of Koch’s postulates: part 1. Am J Gastroenterol. 2010;105:718–721.

    Article  PubMed  Google Scholar 

  32. Spiegel BM, Chey WD, Chang L. Bacterial overgrowth and irritable bowel syndrome: unifying hypothesis or a spurious consequence of proton pump inhibitors? Am J Gastroenterol. 2008;103:2972–2976.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Bruno G, Zaccari P, Rocco G et al. Proton pump inhibitors and dysbiosis: Current knowledge and aspects to be clarified. World J Gastroenterol. 2019;25:2706–2719.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Giamarellos-Bourboulis EJ, Pyleris E, Barbatzas C, Pistiki A, Pimentel M. Small intestinal bacterial overgrowth is associated with irritable bowel syndrome and is independent of proton pump inhibitor usage. BMC Gastroenterol. 2016;16:67.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Pimentel M, Saad RJ, Long MD, Rao SSC. ACG Clinical Guideline: Small intestinal bacterial overgrowth. Am J Gastroenterol 2020;115:165–178.

    Article  PubMed  Google Scholar 

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No specific grants were received from public sector agencies, the business sector, or nonprofit organizations in relation to this study.

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Authors and Affiliations



JMRT acts as guarantor of the article. CDR and JMRT wrote the paper. JMRT, JAVRV, and MAB designed the research study and analyzed the data. CDR, BAPP, LAMJ, EMC, ATR, and CAAR performed the research and collected the data. All authors approved the final version of the article, including the authorship list.

Corresponding author

Correspondence to José María Remes-Troche.

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Conflict of interest

JMRT has served as advisory board for Takeda, Asofarma, and Biocodex, and is also a speaker for Takeda, Asofarma, Alfasigma, Carnot, Chinoin, Medtronic, Ferrer, and Sanofi. MAB and JAVRV are speakers for Takeda and Asofarma. CDR has received and educational grant form Medtronic. BAPP, LAMJ, EMC, ATR, and CAAR do not have conflict of interest.

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Protection of human and animal subjects: The authors declare that no experiments were performed on humans or animals for this study. Confidentiality of data: The authors declare that no patient data appear in this article.

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Durán-Rosas, C., Priego-Parra, B.A., Morel-Cerda, E. et al. Incidence of Small Intestinal Bacterial Overgrowth and Symptoms After 7 Days of Proton Pump Inhibitor Use: A Study on Healthy Volunteers. Dig Dis Sci 69, 209–215 (2024).

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