Bacterial Overgrowth and Irritable Bowel Syndrome: Unifying Hypothesis or a Spurious Consequence of Proton Pump Inhibitors?
Open accessAbstract
Some studies indicate that small intestinal bacterial overgrowth (SIBO), as measured by hydrogen breath tests (HBT), is more prevalent in patients with irritable bowel syndrome (IBS) vs. matched controls without IBS. Although the data are conflicting, this observation has led to the hypothesis that SIBO may be a primary cause of IBS. Yet, it remains unclear whether SIBO is truly fundamental to the pathophysiology of IBS, or is instead a mere epiphenomenon or bystander of something else altogether. We hypothesize that SIBO might be a byproduct of the disproportionate use of proton pump inhibitors (PPIs) in IBS, as follows: (1) IBS patients are more likely than controls to receive PPI therapy; (2) PPI therapy may promote varying forms of SIBO by eliminating gastric acid; and (3) existing studies linking SIBO to IBS have not adjusted for or excluded the use of PPI therapy. When linked together, these premises form the basis for a simple and testable hypothesis: the relationship between SIBO and IBS may be confounded by PPIs. Our article explores these premises, lays out the argument supporting this "PPI hypothesis," discusses potential implications, and outlines next steps to further investigate this possibility.
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Chronic treatment with PPIs strongly impacts small intestine microbiota and, in particular, causes small intestinal bacterial overgrowth (SIBO), likely due to the loss of the gastric acid defensive barrier.
“Chronic treatment with PPIs strongly impacts small intestine microbiota and, in particular, causes small intestinal bacterial overgrowth (SIBO), likely due to the loss of the gastric acid defensive barrier[81-83].”
From Proton pump inhibitors and dysbiosis: current knowledge and aspects to be clarified (2019) · cites this paper as [82]
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Cites
Longstreth, G. F., Thompson, W. G., Chey, W. D., Houghton, L. A., Mearin, F., & Spiller, R. C. (2006) · Gastroenterology · doi:10.1053/j.gastro.2005.11.061 · Cited by 4,856 · see citing works
Self-citationEffects of a Mediterranean-Style Diet on Cardiovascular Risk Factors: A Randomized Trial
Estruch, R., Martínez-González, M. Á., Corella, D., Salas-Salvadó, J., Ruiz-Gutiérrez, V., Covas, M. I., Fiol, M., Gómez-Gracia, E., López-Sabater, M. C., Vinyoles, E., et al. (2006) · Annals of Internal Medicine · doi:10.7326/0003-4819-145-1-200607040-00004 · Cited by 1,704 · see citing works
Kassinen, A., Krogius-Kurikka, L., Mäkivuokko, H., Rinttilä, T., Paulin, L., Corander, J., Malinen, E., Apajalahti, J., & Palva, A. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.04.005 · Cited by 1,002 · see citing works
Dial, S. (2005) · JAMA · doi:10.1001/jama.294.23.2989 · Cited by 954 · see citing works
Eradication of Small Intestinal Bacterial Overgrowth Reduces Symptoms of Irritable Bowel Syndrome
Pimentel, M., Chow, E. J., & Lin, H. C. (2000) · American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2000.03368.x · Cited by 780 · see citing works
Pimentel, M., Chow, E. J., & Lin, H. C. (2003) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2003.07234.x · Cited by 670 · see citing works
Drossman, D. A., Toner, B. B., Whitehead, W. E., Diamant, N. E., Dalton, C. B., Duncan, S., Emmott, S., Proffitt, V., Akman, D., Frusciante, K., et al. (2003) · Gastroenterology · doi:10.1016/s0016-5085(03)00669-3 · Cited by 614 · see citing works
Small intestinal bacterial overgrowth in patients with irritable bowel syndrome
Posserud, I., Stotzer, P.-O., Björnsson, E. S., Abrahamsson, H., & Simrén, M. (2007) · Gut · doi:10.1136/gut.2006.108712 · Cited by 499 · cited 3× · see citing works
“More recently, Posserud and colleagues found no difference in jejunal aspirate yield between IBS and control patients when adopting the 105 colony forming units (CFU) threshold, but did find that mildly increased bacterial counts (using a lower 103 CFU cut off) were more common in IBS than controls (10).”
BackgroundPimentel, M., Park, S., Mirocha, J., Kane, S. V., & Kong, Y. (2006) · Annals of Internal Medicine · doi:10.7326/0003-4819-145-8-200610170-00004 · Cited by 466 · see citing works
A controlled trial of psychological treatment for the irritable bowel syndrome
Guthrie, E., Creed, F. H., Dawson, D., & Tomenson, B. (1991) · Gastroenterology · doi:10.1016/0016-5085(91)90215-7 · Cited by 461 · see citing works
Small Intestinal Bacterial Overgrowth: A Framework for Understanding Irritable Bowel Syndrome
Lin, H. C. (2004) · JAMA · doi:10.1001/jama.292.7.852 · Cited by 396 · see citing works
Sharara, A. I., Aoun, E., Abdul-Baki, H., Mounzer, R., Sidani, S., & ElHajj, I. (2006) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2006.00458.x · Cited by 344 · see citing works
Thorens, J.-J., Froehlich, F., Schwizer, W., Saraga, E. P., Billé, J., Gyr, K. E., Duroux, P., Nicolet, M., Pignatelli, B., Blum, A. L., et al. (1996) · Gut · doi:10.1136/gut.39.1.54 · Cited by 339 · see citing works
Overlap of gastrointestional symptom complexes in a US community
Locke, G., Zinsmeister, A., Fett, S., Melton, L., & Talley, N. (2005) · Neurogastroenterology and Motility · doi:10.1111/j.1365-2982.2004.00581.x · Cited by 254 · see citing works
Laine, Ahnen, Mcclain, Solcia, & Walsh (2000) · Alimentary Pharmacology & Therapeutics · doi:10.1046/j.1365-2036.2000.00768.x · Cited by 247 · see citing works
Talley, N. J., Dennis, E. H., Schettler-Duncan, V. A., Lacy, B. E., Olden, K. W., & Crowell, M. D. (2003) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2003.07699.x · Cited by 239 · see citing works
Review article: proton pump inhibitors and bacterial overgrowth
Williams, C., & McColl, K. E. L. (2005) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2006.02707.x · Cited by 219 · see citing works
Theisen, J., Nehra, D., Citron, D. M., Johansson, J., Hagen, J. A., Crookes, P. F., DeMeester, S. R., Bremner, C. G., DeMeester, T. R., & Peters, J. H. (2000) · Journal of Gastrointestinal Surgery · doi:10.1016/s1091-255x(00)80032-3 · Cited by 216 · see citing works
Nucera, G., Gabrielli, M., Lupascu, A., Lauritano, E. C., Santoliquido, A., Cremonini, F., Cammarota, G., Tondi, P., Pola, P., Gasbarrini, G., et al. (2005) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2005.02493.x · Cited by 204 · see citing works
Whiting, P. F., Westwood, M. E., Bojke, L., Palmer, S., Richardson, G. A., Cooper, J., Watt, I. S., Glanville, J., Sculpher, M. J., & Kleijnen, J. (2006) · Health Technology Assessment · doi:10.3310/hta10360 · Cited by 201 · see citing works
Duodenal bacterial overgrowth during treatment in outpatients with omeprazole.
Fried, M., Siegrist, H. H., Frei, R., Froehlich, F., Duroux, P., Thorens, J.-J., Blum, A. L., Billé, J., Gonvers, J. J., & Gyr, K. E. (1994) · Gut · doi:10.1136/gut.35.1.23 · Cited by 200 · see citing works
Cognitive therapy for irritable bowel syndrome.
Greene, B., & Blanchard, E. B. (1994) · Journal of Consulting and Clinical Psychology · doi:10.1037//0022-006x.62.3.576 · Cited by 188 · see citing works
Lupascu, A., Gabrielli, M., Lauritano, E. C., Scarpellini, E., Santoliquido, A., Cammarota, G., Flore, R. A., Tondi, P., POLA, P., Gasbarrini, G. B., et al. (2005) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2005.02690.x · Cited by 186 · see citing works
Payne, A., & Blanchard, E. B. (1995) · Journal of Consulting and Clinical Psychology · doi:10.1037/0022-006x.63.5.779 · Cited by 186 · see citing works
Walters, B., & Vanner, S. J. (2005) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2005.40795.x · Cited by 172 · see citing works
Coyle, W. (2006) · Current Gastroenterology Reports · doi:10.1007/s11894-006-0050-4 · Cited by 171 · see citing works
Payne, A., & Blanchard, E. B. (1995) · Journal of Consulting and Clinical Psychology · doi:10.1037//0022-006x.63.5.779 · Cited by 166 · see citing works
Altered bowel function and duodenal bacterial overgrowth in patients treated with omeprazole
Lewis, S. J., Franco, S. S. D. R., Young, G. O., & O’Keefe, S. J. (1996) · Alimentary Pharmacology & Therapeutics · doi:10.1046/j.1365-2036.1996.d01-506.x · Cited by 151 · see citing works
Two controlled evaluations of multicomponent psychological treatment of irritable bowel syndrome
Blanchard, E. B., Schwarz, S. P., Suls, J. M., Gerardi, M. A., Scharff, L., Greene, B., Taylor, A. E., Berreman, C. F., & Malamood, H. S. (1992) · Behaviour Research and Therapy · doi:10.1016/0005-7967(92)90141-3 · Cited by 148 · see citing works
Cognitive therapy for irritable bowel syndrome.
Greene, B., & Blanchard, E. B. (1994) · Journal of Consulting and Clinical Psychology · doi:10.1037/0022-006x.62.3.576 · Cited by 140 · see citing works
Stress Management for Irritable Bowel Syndrome: A Controlled Trial
Shaw, G., Srivastava, E. D., Sadlier, M., Swann, P., James, J., & Rhodes, J. (2009) · Digestion · doi:10.1159/000200738 · Cited by 125 · see citing works
A multi-component treatment for irritable bowel syndrome
Neff, D. F., & Blanchard, E. B. (1987) · Behavior Therapy · doi:10.1016/s0005-7894(87)80052-7 · Cited by 119 · see citing works
Keefer, L., & Blanchard, E. B. (2001) · Behaviour Research and Therapy · doi:10.1016/s0005-7967(00)00078-4 · Cited by 104 · see citing works
Majewski, M. S., & McCallum, R. W. (2007) · PubMed · Cited by 101 · see citing works
NOJKOV, B., RUBENSTEIN, J. H., ADLIS, S. A., SHAW, M. J., SAAD, R., RAI, J., WEINMAN, B., & CHEY, W. D. (2008) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2008.03596.x · Cited by 101 · see citing works
Self-citationStudying the Overlap Between IBS and GERD: A Systematic Review of the Literature
Nastaskin, I., Mehdikhani, E., Conklin, J., Park, S., & Pimentel, M. (2006) · Digestive Diseases and Sciences · doi:10.1007/s10620-006-9306-y · Cited by 98 · see citing works
Kennedy, T., Chalder, T., McCrone, P., Darnley, S., Knapp, M., Jones, R., & Wessely, S. (2006) · Health Technology Assessment · doi:10.3310/hta10190 · Cited by 92 · see citing works
A controlled behavioral treatment study of Irritable Bowel syndrome
Lynch, P. M., & Zamble, E. (1989) · Behavior Therapy · doi:10.1016/s0005-7894(89)80130-3 · Cited by 78 · see citing works
Tkachuk, G. A., Graff, L. A., Martin, G. L., & Bernstein, C. N. (2003) · Journal of Clinical Psychology in Medical Settings · doi:10.1023/a:1022809914863 · Cited by 62 · see citing works
Clinical trial: short‐ and long‐term benefit of relaxation training for irritable bowel syndrome
van der Veek, P. P. J., van Rood, Y. R., & Masclee, A. (2007) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2007.03437.x · Cited by 59 · see citing works
Breath Tests for Gastrointestinal Disease: The Real Deal or Just a Lot of Hot Air?
Saad, R. J., & Chey, W. D. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.10.059 · Cited by 47 · see citing works
Self-citationTreatment for Bacterial Overgrowth in the Irritable Bowel Syndrome
Drossman, D. A. (2006) · Annals of Internal Medicine · doi:10.7326/0003-4819-145-8-200610170-00012 · Cited by 24 · see citing works
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- [7]Pimentel M Trivieri L Help at last: The Cedars-Sinai protocol for treating IBS A new IBS solution 69 90 Health Point Press Sherman Oaks, CA
Cited by
Sorted by citations
Ford, A. C., Spiegel, B. M. R., Talley, N. J., & Moayyedi, P. (2009) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2009.06.031 · Cited by 351 · see citing works
Self-citationIncreased Incidence of Small Intestinal Bacterial Overgrowth During Proton Pump Inhibitor Therapy
Lombardo, L., Foti, M., Ruggia, O., & Chiecchio, A. (2010) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2009.12.022 · Cited by 350 · see citing works
Proton Pump Inhibitor Use and the Risk of Small Intestinal Bacterial Overgrowth: A Meta-analysis
Lo, W., & Chan, W. W. (2013) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2012.12.011 · Cited by 353 · see citing works
Proton pump inhibitors and dysbiosis: current knowledge and aspects to be clarified
Bruno, G., Zaccari, P., Rocco, G., Scalese, G., Panetta, C., Porowska, B., Pontone, S., & Severi, C. (2019) · World Journal of Gastroenterology · doi:10.3748/wjg.v25.i22.2706 · Cited by 258 · see citing works
Compare, D., Pica, L., Rocco, A., De Giorgi, F., Cuomo, R., Sarnelli, G., Romano, M., & Nardone, G. (2011) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.2010.02419.x · Cited by 122 · see citing works
Chen, B., Kim, J. J.-W., Zhang, Y., Du, L., & Dai, N. (2018) · Journal of Gastroenterology · doi:10.1007/s00535-018-1476-9 · Cited by 117 · see citing works
Lovell, R. M., & Ford, A. C. (2012) · American Journal of Gastroenterology · doi:10.1038/ajg.2012.336 · Cited by 95 · see citing works
Marlicz, W., Łoniewski, I., Grimes, D. S., & Quigley, E. M. (2014) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2014.07.015 · Cited by 91 · see citing works
What are the effects of proton pump inhibitors on the small intestine?
Fujimori, S. (2015) · World Journal of Gastroenterology · doi:10.3748/wjg.v21.i22.6817 · Cited by 70 · see citing works
Spiegel, B. M. R. (2011) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2011.02.030 · Cited by 67 · see citing works
Self-citationLaw, D., & Pimentel, M. (2010) · Digestive Diseases and Sciences · doi:10.1007/s10620-009-1010-2 · Cited by 35 · see citing works
Schmulson, M. J., & Frati-Munari, A. C. (2019) · Revista de Gastroenterología de México · doi:10.1016/j.rgmx.2018.02.008 · Cited by 14 · see citing works
- Authors
- Spiegel, B. M. R., Chey, W. D., & Chang, L.
- Affiliations
- University of California, Los Angeles (US)
- University of Michigan (US)
- Corresponding author
- Spiegel, Brennan M.R.
- Venue
- The American Journal of Gastroenterology
- Published
- 2008-12
- Volume
- 103
- Issue
- 12
- Pages
- 2972-2976
- ISSN
- 0002-9270 (ISSN-L)
- 1572-0241
- PMC
- PMC2949084
- OpenAlex
- W2061874852
- Cited by
- 95
- References
- 42
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 6 · 2022: 5 · 2021: 7 · 2020: 6 · 2019: 4 · 2018: 4 · 2017: 3 · 2015: 5 · 2014: 3 · 2013: 7 · 2012: 11
- FWCI
- 9.99
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The American Journal of Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (P50DK064539, P30DK041301)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR46122-01, R01AR046122)
- National Center for Complementary and Integrative Health (R24AT002681)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastroesophageal reflux and treatments
- Keywords
- small intestinal bacterial overgrowth, irritable bowel syndrome, proton pump inhibitors, hydrogen breath test, gastric acid suppression, confounding, IBS pathophysiology, SIBO prevalence
- MeSH terms
- Bacteria, Humans, Intestine, Small, Irritable Bowel Syndrome, Proton Pump Inhibitors
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