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Proton pump inhibitor use is not independently associated with colonic diverticulosis in an asymptomatic screening population
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  • Published: 26 January 2026

Proton pump inhibitor use is not independently associated with colonic diverticulosis in an asymptomatic screening population

  • Andreas Völkerer1,
  • Sarah Wernly1,
  • Georg Semmler2,
  • Maria Flamm3,
  • Mathias Ausserwinkler4,6,
  • Gabriele Koch1,
  • Nikolaus Götz5,
  • Hannah Hofer1,
  • Elmar Aigner6,
  • Christian Datz1 na1 &
  • …
  • Bernhard Wernly3,6 na1 

Scientific Reports , Article number:  (2026) Cite this article

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We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Drug regulation
  • Gastrointestinal diseases

Abstract

Proton pump inhibitors (PPIs) are widely used medications that alter gut microbiota. Given the high prevalence of colonic diverticulosis and its increasing incidence in younger populations, we investigated whether PPI use is associated with diverticulosis prevalence in an asymptomatic screening population. This retrospective observational study analyzed data from 6,153 asymptomatic individuals undergoing colorectal cancer screening in Austria. Colonoscopies assessed diverticulosis presence, while PPI use was determined via structured medical history. Statistical analyses, including Poisson regression models and sensitivity analyses, were conducted to evaluate the association between PPI use and diverticulosis, with adjustments for confounding factors such as age, sex, BMI, comorbidities, and lifestyle characteristics. Among 6,153 participants, 37% were found to have diverticulosis, with a significantly higher prevalence observed in PPI users (48%) compared to non-users (36%, p < 0.001). PPI users were generally older, had a higher BMI, and were more likely to have cardiometabolic comorbidities. Univariate analysis demonstrated a significant association between PPI use and diverticulosis (RR 1.326, 95% CI: 1.199–1.476, p < 0.001). However, this association was not sustained in multivariable models adjusted for age, sex, BMI, comorbidities, and lifestyle factors, indicating that the observed relationship is likely attributable to confounding rather than a direct causal effect. In this large screening cohort, the initially observed association between PPI use and diverticulosis was likely attributable to confounding. These findings suggest that PPI use is not independently associated with diverticulosis.

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Data availability

Data is provided within the manuscript.

References

  1. Strand, D. S., Kim, D. & Peura, D. A. 25 years of proton pump inhibitors: A comprehensive review. Gut Liver. 11, 27–37 (2017).

    Google Scholar 

  2. Ang, S. P. et al. Association between proton pump inhibitor use and risk of incident chronic kidney disease: systematic review and Meta-Analysis. Biomedicines 12 https://doi.org/10.3390/biomedicines12071414 (2024).

  3. Edinoff, A. N. et al. Proton pump Inhibitors, kidney Damage, and mortality: an updated narrative review. Adv. Ther. 40, 2693–2709 (2023).

    Google Scholar 

  4. Ito, T. & Jensen, R. T. Association of Long-Term proton pump inhibitor therapy with bone fractures and effects on absorption of Calcium, vitamin B12, Iron, and magnesium. Curr. Gastroenterol. Rep. 12, 448–457 (2010).

    Google Scholar 

  5. Hojo, M. et al. Gut microbiota composition before and after use of proton pump inhibitors. Dig. Dis. Sci. 63, 2940–2949 (2018).

    Google Scholar 

  6. Jackson, M. A. et al. Proton pump inhibitors alter the composition of the gut microbiota. Gut 65, 749–756 (2016).

    Google Scholar 

  7. Tursi, A. et al. Colonic diverticular disease. Nat. Rev. Dis. Primers. 6, 20 (2020).

    Google Scholar 

  8. Imaeda, H. & Hibi, T. The burden of diverticular disease and its complications: West versus East. Inflamm. Intest Dis. 3, 61–68 (2018).

    Google Scholar 

  9. Soh, Y. S. A. et al. Rising prevalence of colonic diverticulosis in a Westernized Multi-Ethnic Asian community. J. Gastroenterol. Hepatol. 36, 413–420 (2021).

    Google Scholar 

  10. Schultz, J. K. et al. European society of coloproctology: guidelines for the management of diverticular disease of the colon. Colorectal Dis. 22 (Suppl 2), 5–28 (2020).

    Google Scholar 

  11. Munie, S. T. & Nalamati, S. P. M. Epidemiology and pathophysiology of diverticular disease. Clin. Colon Rectal Surg. 31, 209–213 (2018).

    Google Scholar 

  12. Etzioni, D. A., Mack, T. M., Beart, R. W. & Kaiser, J. Diverticulitis in the united states: 1998–2005: changing patterns of disease and treatment. Ann. Surg. 249, 210 (2009).

    Google Scholar 

  13. Peery, A. F. et al. Colonic diverticula are not associated with mucosal inflammation or chronic Gastrointestinal symptoms. Clin. Gastroenterol. Hepatol. 16, 884–891e1 (2018).

    Google Scholar 

  14. Violi, A. et al. Epidemiology and risk factors for diverticular disease. Acta Biomed. 89, 107–112 (2018).

    Google Scholar 

  15. Schafmayer, C. et al. Genome-Wide association analysis of diverticular disease points towards Neuromuscular, connective tissue and epithelial pathomechanisms. Gut 68, 854–865 (2019).

    Google Scholar 

  16. Peery, A. F. et al. Distribution and characteristics of colonic diverticula in a united States screening population. Clin. Gastroenterol. Hepatol. 14, 980–985e1 (2016).

    Google Scholar 

  17. Völkerer, A. et al. Diverticulosis and cardiometabolic risk factors: A systematic literature review. Int. J. Colorectal Dis. 38, 236 (2023).

    Google Scholar 

  18. Wlodarczyk, J. R. et al. Prevalence of and risk factors for incidental colonic diverticulosis. J. Surg. Res. 280, 348–354 (2022).

    Google Scholar 

  19. Peery, A. F. Colonic diverticula and diverticular disease: 10 facts clinicians should know. N C Med. J. 77, 220–222 (2016).

    Google Scholar 

  20. Tursi, A. et al. Risk factors for endoscopic severity of diverticular disease of the colon and its outcome: A Real-Life Case-Control study. Eur. J. Gastroenterol. Hepatol. 32, 1123–1129 (2020).

    Google Scholar 

  21. Sbeit, W. et al. Proton pump inhibitor use May increase the risk of diverticulitis but not it’s severity among patients with colonic diverticulosis: A multicenter study. J. Clin. Med. 9 https://doi.org/10.3390/jcm9092966 (2020).

  22. Mastoraki, A. et al. Evaluation of molecular and genetic predisposing parameters at diverticular disease of the colon. Int. J. Colorectal Dis. 36, 903–910 (2021).

    Google Scholar 

  23. Tursi, A. Current and evolving concepts on the pathogenesis of diverticular disease. J. Gastrointestin Liver Dis. 28, 225–235 (2019).

    Google Scholar 

  24. Peery, A. F. et al. Burden and cost of Gastrointestinal, Liver, and pancreatic diseases in the united states: update 2021. Gastroenterology 162, 621–644 (2022).

    Google Scholar 

  25. Putz, E. & Senn, S. Bevölkerung im Land Salzburg: Stand & Entwicklung 2021. Amt der Salzburger Landesregierung, Landesstatistik und Verwaltungscontrolling, Salzburg, Austria, ; ISBN 978-3-902982-99-5. (2021).

  26. Wernly, S. et al. Sex-specific propensity-adjusted analysis of colonic adenoma detection rates in a screening cohort. Sci. Rep. 11, 17785 (2021).

    Google Scholar 

  27. Williams, B. et al. 2018 ESC/ESH guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European society of cardiology (ESC) and the European society of hypertension (ESH). Eur. Heart J. 39, 3021–3104 (2018).

    Google Scholar 

  28. Alberti, K. G. M. M. et al. Harmonizing the metabolic syndrome: A joint interim statement of the international diabetes federation task force on epidemiology and Prevention; National heart, Lung, and blood Institute; American heart association; world heart federation; international atherosclerosis Society; and international association for the study of obesity. Circulation 120, 1640–1645 (2009).

    Google Scholar 

  29. Bisschops, R. et al. Performance measures for upper Gastrointestinal endoscopy: A European society of Gastrointestinal endoscopy (ESGE) quality improvement initiative. Endoscopy 48, 843–864 (2016).

    Google Scholar 

  30. Storz, C. et al. Characteristics and associated risk factors of diverticular disease assessed by magnetic resonance imaging in subjects from a Western general population. Eur. Radiol. 29, 1094–1103 (2019).

    Google Scholar 

  31. Mashayekhi, R. et al. Obesity, but not physical Activity, is associated with higher prevalence of asymptomatic diverticulosis. Clin. Gastroenterol. Hepatol. 16, 586–587 (2018).

    Google Scholar 

  32. Lee, S. P., Ahn, Y. W., Lee, O. Y. & Lee, K. N. The relationship between colonic diverticulosis and abdominal visceral and subcutaneous fat accumulation measured by abdominal CT scan. Turk. J. Gastroenterol. 25, 192–197 (2014).

    Google Scholar 

  33. Bae, H. J. et al. Risk factors for asymptomatic colon diverticulosis. Korean J. Gastroenterol. 74, 142–148 (2019).

    Google Scholar 

  34. Comstock, S. S. et al. Cross-Sectional analysis of obesity and serum analytes in males identifies sRAGE as a novel biomarker inversely associated with diverticulosis. PLoS One 9, e95232. (2014).

  35. Teixeira, C. et al. Colonic diverticulosis and the metabolic syndrome: an association? Rev. Esp. Enferm Dig. 109, 768–771 (2017).

    Google Scholar 

  36. Yeo, L. X. et al. Hypertension control and risk of colonic diverticulosis. Th. Adv. Gastroenterol. 12, 1756284819855734 (2019).

    Google Scholar 

  37. Braunschmid, T. et al. Constipation is not associated with diverticular Disease - Analysis of 976 patients. Int. J. Surg. 19, 42–45 (2015).

    Google Scholar 

  38. Völkerer, A. et al. The impact of educational status on the occurrence of colonic diverticula: insights from an Austrian cohort study. Med. Princ Pract. 33, 242–250 (2024).

    Google Scholar 

  39. Ho, B. L., Hu, H. Y. & Chang, S. S. Association between use of proton pump inhibitors and occurrence of colon diverticulitis. J. Chin. Med. Assoc. 79, 5–10 (2016).

    Google Scholar 

  40. Tian, L. et al. Proton pump inhibitors May enhance the risk of digestive diseases by regulating intestinal microbiota. Front. Pharmacol. 14, 1217306 (2023).

    Google Scholar 

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Author information

Author notes
  1. These authors contributed equally: Christian Datz and Bernhard Wernly .

Authors and Affiliations

  1. Department of Internal Medicine, General Hospital Oberndorf, Teaching Hospital of the Paracelsus Medical University, Salzburg, Austria

    Andreas Völkerer, Sarah Wernly, Gabriele Koch, Hannah Hofer & Christian Datz

  2. Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria

    Georg Semmler

  3. Family Medicine and Preventive Medicine, Center for Public Health and Healthcare Research, Institute of General Practice, Paracelsus Medical University, Salzburg, Austria

    Maria Flamm & Bernhard Wernly

  4. Department of Internal Medicine, Elisabethinen Hospital Klagenfurt, Klagenfurt, Austria

    Mathias Ausserwinkler

  5. Department of Internal Medicine, General Hospital, St. Vinzenz Zams, Zams, Austria

    Nikolaus Götz

  6. First Department of Medicine, University Clinic Salzburg, Paracelsus Medical University Salzburg, Salzburg, Austria

    Mathias Ausserwinkler, Elmar Aigner & Bernhard Wernly

Authors
  1. Andreas Völkerer
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  2. Sarah Wernly
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Contributions

Andreas Völkerer and Bernhard Wernly conceived the research project. Gabriele Koch helped to collect and organize the raw data. Bernhard Wernly conducted the statistical analysis. Andreas Völkerer wrote the first draft of the manuscript. Bernhard Wernly, Sarah Wernly, Georg Semmler, Mathias Ausserwinkler, Nikolaus Götz, Hannah Hofer, Maria Flamm, Elmar Aigner and Christian Datz provided critical feedback and improved the manuscript. All authors reviewed the manuscript.

Corresponding author

Correspondence to Bernhard Wernly.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics statement

We performed the study and all procedures according to the principles of the Declaration of Helsinki. The local ethics committee for the province Salzburg approved the study protocol (approval no. 415-E/1262). Written informed consent was obtained from every participant.

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Völkerer, A., Wernly, S., Semmler, G. et al. Proton pump inhibitor use is not independently associated with colonic diverticulosis in an asymptomatic screening population. Sci Rep (2026). https://doi.org/10.1038/s41598-026-37547-2

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  • Received: 10 March 2025

  • Accepted: 22 January 2026

  • Published: 26 January 2026

  • DOI: https://doi.org/10.1038/s41598-026-37547-2

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Keywords

  • Diverticulosis
  • Diverticular disease
  • PPI
  • Microbiome
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