Questioning the Bacterial Overgrowth Hypothesis of Irritable Bowel Syndrome: An Epidemiologic and Evolutionary Perspective
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Although studies indicate that small intestinal bacterial overgrowth (SIBO) is prevalent in irritable bowel syndrome (IBS), it remains unclear whether SIBO causes IBS. This review presents an epidemiologic and evolutionary inquiry that questions the bacterial overgrowth hypothesis of IBS, as follows. (1) Although the hypothesis may be biologically plausible, there is also a strong rationale for competing hypotheses; it is unlikely that SIBO is the predominant cause of IBS in all comers, because competing explanations are sensible and defensible. Moreover, data indicate that the test used to promulgate the SIBO hypothesis - the lactulose hydrogen breath test - may not have measured SIBO in the first place. (2) We do not have evidence of SIBO being absent before IBS symptoms, and present after IBS emerges. (3) There is not a dose-response relationship between small intestinal microbiota and IBS symptoms. (4) The relationship between SIBO and IBS is highly inconsistent among studies. (5) Many effective IBS therapies do not address SIBO at all, yet have a more favorable "number needed to treat" than antibiotics. (6) IBS does not behave like a traditional infectious disease, suggesting that microbes may not principally cause the syndrome. (7) Other factors may confound the relationship between SIBO and IBS, including proton pump inhibitors. (8) Whereas the brain-gut hypothesis is evolutionary sensible, the bacterial hypothesis is harder to defend from an evolutionary perspective. The article concludes that bacteria may contribute to some IBS symptoms, but that bacteria cannot be the only explanation, and a causal link between SIBO and IBS is not secure.
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The large differences between studies, methodological problems such as lack of standardization, poor sensitivity and specificity of breath tests, and the questioned cutoff value of cultured duodenum/jejunum aspirates make the importance of SIBO in IBS unclear.
“However, the large differences between the studies, methodological problems, such as the lack of standardization, poor sensitivity and specificity of breath tests, as well as the questioned cutoff value of cultured duodenum/jejunum aspirates (> 10 5 CFU/mL), make the importance of SIBO in IBS unclear [56] .”
From Intestinal microbiota in health and disease: Role of bifidobacteria in gut homeostasis (2014) · cites this paper as [56]
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Gastrointestinal microbiome signatures of pediatric patients with irritable bowel syndrome
Saulnier, D. M., Riehle, K., Mistretta, T., Diaz, M., Mandal, D., Raza, S., Weidler, E. M., Qin, X., Coarfa, C., Milosavljevic, A., et al. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.06.072 · Cited by 672 · see citing works
Ford, A. C., Moayyedi, P., Lacy, B. E., Lembo, A. J., Saito, Y. A., Schiller, L. R., Soffer, E., Spiegel, B. M. R., & Quigley, E. M. M. (2014) · The American Journal of Gastroenterology · doi:10.1038/ajg.2014.187 · Cited by 648 · see citing works
Self-citationIntestinal microbiota in health and disease: Role of bifidobacteria in gut homeostasis
Tojo, R. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i41.15163 · Cited by 533 · see citing works
Irritable bowel syndrome: Pathogenesis, diagnosis, treatment, and evidence-based medicine
Saha, L. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i22.6759 · Cited by 500 · see citing works
A role for the gut microbiota in IBS
Collins, S. M. (2014) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2014.40 · Cited by 351 · see citing works
The Intestinal Microenvironment and Functional Gastrointestinal Disorders
Barbara, G., Feinle-Bisset, C., Ghoshal, U. C., Santos, J., Vanner, S. J., Vergnolle, N., Zoetendal, E. G., & Quigley, E. M. (2016) · Gastroenterology · doi:10.1053/j.gastro.2016.02.028 · Cited by 335 · see citing works
Contributions of the microbial hydrogen economy to colonic homeostasis
Carbonero, F. G., Benefiel, A. C., & Gaskins, H. R. (2012) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2012.85 · Cited by 291 · see citing works
Irritable bowel syndrome: A clinical review
Soares, R. L. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i34.12144 · Cited by 266 · see citing works
The microbiota-gut-brain axis in functional gastrointestinal disorders
De Palma, G., Collins, S. M., & Bercik, P. (2014) · Gut Microbes · doi:10.4161/gmic.29417 · Cited by 157 · see citing works
A Gastroenterologist's Guide to Probiotics
Ciorba, M. A. (2012) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2012.03.024 · Cited by 150 · see citing works
Irritable bowel syndrome: the clinical approach
Adriani, A., Ribaldone, D. G., Astegiano, M., Durazzo, M., Saracco, G. M., & Pellicano, R. (2018) · Panminerva Medica · doi:10.23736/s0031-0808.18.03541-3 · Cited by 149 · see citing works
Gut Microbiota as Potential Orchestrators of Irritable Bowel Syndrome
Bennet, S., Öhman, L., & Simrén, M. (2015) · Gut and Liver · doi:10.5009/gnl14344 · Cited by 143 · see citing works
Small Intestinal Bacterial Overgrowth
Quigley, E. M. M., & Abu-Shanab, A. (2010) · Infectious Disease Clinics of North America · doi:10.1016/j.idc.2010.07.007 · Cited by 108 · see citing works
Microflora Modulation of Motility
Quigley, E. M. M. (2011) · Journal of Neurogastroenterology and Motility · doi:10.5056/jnm.2011.17.2.140 · Cited by 106 · see citing works
Walker, M. M., & Talley, N. J. (2014) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.12666 · Cited by 101 · see citing works
Small intestinal bacterial overgrowth
Quigley, E. M. M. (2014) · Current Opinion in Gastroenterology · doi:10.1097/mog.0000000000000040 · Cited by 96 · see citing works
Pinn, D. M., Aroniadis, O. C., & Brandt, L. J. (2014) · Neurogastroenterology & Motility · doi:10.1111/nmo.12479 · Cited by 91 · see citing works
Upper gastrointestinal microbiota and digestive diseases
Wang, Z.-K. (2013) · World Journal of Gastroenterology · doi:10.3748/wjg.v19.i10.1541 · Cited by 88 · see citing works
Evaluation of Harm in the Pharmacotherapy of Irritable Bowel Syndrome
Shah, E. D., Kim, S., Chong, K., Lembo, A. J., & Pimentel, M. (2012) · The American Journal of Medicine · doi:10.1016/j.amjmed.2011.08.026 · Cited by 80 · see citing works
Probiotics in the Management of Functional Bowel Disorders
Quigley, E. M. M. (2012) · Gastroenterology Clinics of North America · doi:10.1016/j.gtc.2012.08.005 · Cited by 77 · see citing works
Unraveling the ties between irritable bowel syndrome and intestinal microbiota
Hong, S. N. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i10.2470 · Cited by 75 · see citing works
Miazga, A., Osiński, M., Cichy, W., & Żaba, R. W. (2014) · Advances in Medical Sciences · doi:10.1016/j.advms.2014.09.001 · Cited by 59 · see citing works
Gut Microbiota-Based Therapies for Irritable Bowel Syndrome
Stern, E., & Brenner, D. M. (2018) · Clinical and Translational Gastroenterology · doi:10.1038/ctg.2018.2 · Cited by 48 · see citing works
Small Intestinal Bacterial Overgrowth
Bushyhead, D. W., & Quigley, E. M. M. (2021) · Gastroenterology Clinics of North America · doi:10.1016/j.gtc.2021.02.008 · Cited by 48 · see citing works
Small intestinal bacterial overgrowth as a cause for irritable bowel syndrome: guilty or not guilty?
Aziz, I., Törnblom, H., & Simrén, M. (2017) · Current Opinion in Gastroenterology · doi:10.1097/mog.0000000000000348 · Cited by 45 · see citing works
Schmulson, M. J., Bielsa, M. V., Carmona-Sánchez, R., Hernández, A., López‐Colombo, A., López‐Vidal, Y., Peláez‐Luna, M., Remes-Troche, J. M., Tamayo, J. L., & Valdovinos, M. A. (2014) · Revista de Gastroenterología de México (English Edition) · doi:10.1016/j.rgmxen.2014.01.001 · Cited by 38 · see citing works
The Intestinal Microbiota in the Irritable Bowel Syndrome
Collins, S. M. (2016) · International Review of Neurobiology · doi:10.1016/bs.irn.2016.08.003 · Cited by 30 · see citing works
Schmulson, M., Bielsa, M. V., Carmona-Sánchez, R., Hernández, A., López-Colombo, A., López Vidal, Y., Peláez-Luna, M., Remes-Troche, J. M., Tamayo, J. L., & Valdovinos, M. A. (2014) · Revista de Gastroenterología de México · doi:10.1016/j.rgmx.2014.01.004 · Cited by 29 · see citing works
“controles SII Roma II (SII-PI) vs sanos 66 (9) vs 20 Descendente, sigmoides Mastocitos, linfocitos T Descendente LT-CD3, SII: 493 ± 34 vs controles: 587 ± 66, (p = NS); LT-CD8, SII: 388 ± 28 vs controles: 526 ± 50 (p = 0.”
Schatz, R. A., Zhang, Q., Lodhia, N., Shuster, J. J., Toskes, P. P., & Moshiree, B. (2015) · World Journal of Gastroenterology · doi:10.3748/wjg.v21.i15.4574 · Cited by 27 · see citing works
Gut microbiota: an Indicator to Gastrointestinal Tract Diseases
Patel, T., Bhattacharya, P., & Das, S. (2016) · Journal of Gastrointestinal Cancer · doi:10.1007/s12029-016-9820-x · Cited by 24 · see citing works
Current and emerging drug options in the treatment of diarrhea predominant irritable bowel syndrome
Nee, J. W., Zakari, M., & Lembo, A. J. (2015) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.2015.1101449 · Cited by 19 · see citing works
Keszthelyi, D., Dackus, G. M. H. E., Masclee, G. M. C., Kruimel, J. W., & Masclee, A. (2012) · BMC Gastroenterology · doi:10.1186/1471-230x-12-121 · Cited by 19 · see citing works
The Latest Data Concerning the Etiology and Pathogenesis of Irritable Bowel Syndrome
Ionescu, V. A., Gheorghe, G., Georgescu, T. F., Bacalbaşa, N., Gheorghe, F., & Diaconu, C. C. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13175124 · Cited by 19 · see citing works
Ishida, R. K., Faintuch, J., Safatle‐Ribeiro, A. V., Ribeiro, U., & Cecconello, I. (2014) · Obesity Surgery · doi:10.1007/s11695-014-1277-z · Cited by 17 · see citing works
Targeted therapies for diarrhea-predominant irritable bowel syndrome
Olden, K. W. (2012) · Clinical and Experimental Gastroenterology · doi:10.2147/ceg.s29023 · Cited by 15 · see citing works
Role of Small Intestinal Bacterial Overgrowth in Functional Gastrointestinal Disorders
Choi, C. H., & Chang, S. K. (2015) · Journal of Neurogastroenterology and Motility · doi:10.5056/jnm15196 · Cited by 14 · see citing works
Wu, Y., Dai, Y., Zhang, L., Pan, H.-G., Chen, W., Li, R., & Hu, L. (2021) · PLoS ONE · doi:10.1371/journal.pone.0255665 · Cited by 13 · see citing works
The role of rifaximin therapy in patients with irritable bowel syndrome without constipation
Schey, R., & Rao, S. S. C. (2011) · Expert Review of Gastroenterology & Hepatology · doi:10.1586/egh.11.50 · Cited by 10 · see citing works
Thoua, N. M., & Murray, C. D. (2011) · Medicine · doi:10.1016/j.mpmed.2011.01.006 · Cited by 11 · see citing works
Effects of Proton Pump Inhibitor Therapy in the Distal Gut: Putting the Pieces Together
Keszthelyi, D., & Masclee, A. (2012) · Digestive Diseases and Sciences · doi:10.1007/s10620-012-2339-5 · Cited by 7 · see citing works
Management of Small Intestinal Bacterial Overgrowth in Adult Patients
Rasmussen, J., & Duriancik, D. M. (2019) · Gastroenterology Nursing · doi:10.1097/sga.0000000000000369 · Cited by 6 · see citing works
[Irritable Bowel Syndrome; gut microbiota and probiotic therapy].
González, R. T., Gonzalez, A. S., Madiedo, P. R., Mata, A. M., Muniz, M. P., Alonso, E. B., Llorente, F. J. R., Villar, M. C. M., González, M. M. A., Diaz, M. F. V., et al. (2015) · PubMed · doi:10.3305/nh.2015.31.sup1.8713 · Cited by 5 · see citing works
Small intestinal bacterial overgrowth syndrome and irritable bowel syndrome
Gąsiorowska, J., & Czerwionka‐Szaflarska, M. (2013) · Gastroenterology Review · doi:10.5114/pg.2013.36329 · Cited by 4 · see citing works
Small Intestinal Bacterial Overgrowth
Quigley, E. M. M. (2019) · Springer eBooks · doi:10.1007/978-3-030-01117-8_20 · Cited by 4 · see citing works
Methanobrevibacter smithii in irritable bowel syndrome: a clinical and molecular study
Vlasova, A. V., Va, I., Pilipenko, V. I., Sa, S., Markova, Y. M., Сергеевна, П. А., & Maev, I. V. (2019) · Terapevticheskii arkhiv · doi:10.26442/00403660.2019.08.000383 · Cited by 3 · see citing works
Matricon, J. (2012) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.12150 · Cited by 3 · see citing works
Gut Microbiome and Its Role in the Pathophysiology of Irritable Bowel Syndrome
Palma, G. D., & Berčík, P. (2021) · Acta gastroenteorológica latinoamericana/Acta gastroenterológica latinoamericana · doi:10.52787/dxfc9250 · Cited by 4 · see citing works
Clinical Pearls for Irritable Bowel Syndrome
Lacy, B. E., & OʼShana, T. (2014) · Gastroenterology Nursing · doi:10.1097/sga.0000000000000056 · Cited by 2 · see citing works
Clinical predictors of small intestinal bacterial overgrowth by duodenal aspirate culture
Talley, N. J. (2011) · Yearbook of Gastroenterology · doi:10.1016/j.ygas.2011.07.008 · Cited by 2 · see citing works
It is Time to Re-Think the Role of Small Intestinal Bacterial Overgrowth in IBS Patients
Savarino, E. V., Furnari, M., Ottonello, A., & Savarino, V. (2016) · The American Journal of Gastroenterology · doi:10.1038/ajg.2016.290 · Cited by 1 · see citing works
Ali, A., Islam, N., Fakir, N. I., Kabir, A., Sharmin, M., Islam, T., Rahman, M., Badal, F. A., & Taher, A. (2024) · International Journal of Immunology · doi:10.11648/j.iji.20241201.12 · Cited by 1 · see citing works
Mikrobiota und Reizdarmsyndrom – eine kritische Bestandsaufnahme
Enck, P., & Mazurak, N. (2019) · Zeitschrift für Gastroenterologie · doi:10.1055/a-0901-2558 · Cited by 1 · see citing works
Komplementärmedizin im Krankenhaus: Strategien, Konzepte, Umsetzung
Hoefert, H.-W., & Michalsen, A. (2014) · Medizinisch Wissenschaftliche Verlagsgesellschaft eBooks · doi:10.32745/9783954664573 · Cited by 1 · see citing works
Gerson, C. D. (2014) · doi:10.1002/9781118932759.ch34 · Cited by 1 · see citing works
Lasa, J. S., Argüello, M., Dima, G., Peralta, D., & Soifer, L. (2013) · Journal of Gastroenterology and Hepatology Research
Functional Bowel Disorders for the Colorectal Surgeon
Ayscue, J. M., & Kumar, A. S. (2016) · Springer eBooks · doi:10.1007/978-3-319-25970-3_62
Komplementärmedizin in der Gastroenterologie
Hoefert, H.-W. (2014) · Medizinisch Wissenschaftliche Verlagsgesellschaft eBooks · doi:10.32745/9783954664573-1.1
Irritable bowel syndrome and small intestinal bacterial overgrowth: Assessment with breath test
Costa, L., Gomes, T., Braga, C., Lenz, L., Miszputen, S. J., & Ambrogini, O. (2020) · Archives of Clinical Gastroenterology · doi:10.17352/2455-2283.000077
Quigley, E. M. M. (2015) · Wiley eBooks · doi:10.1002/9781118512074.ch66
Irritable Bowel Syndrome: The Functional Medicine Approach
Lacy, S., & Prasad, K. (2023) · Annals of Innovation in Medicine · doi:10.59652/aim.v1i1.32
Irritable bowel syndrome: systematic review of origin, pathology, diagnosis and treatment
Kwiliński, K., Zdunek, R., Strus, K., Madera, M., Kruszewski, A., Dąbrowska, A., Paduszyńska, N., & Wawrzyńska, B. (2024) · Quality in Sport · doi:10.12775/qs.2024.20.53413
Role of microbiota-gut-brain axis in migraine and possible interventions
Raikwar, S., & Jain, S. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-21680-0.00010-9
Nourrisson, C. (2017) · theses.fr (ABES) · doi:10.70675/c54115d2z5b87z4564za955z61887e77ecfe
Danieluk, J., Adamaszek, N., Glinski, M., Kacprzak, U., Dołęga-Mostowska, D., Sochowska, J., Buczkowska, A., Stochaj, L., Flejszman, M., & Wójcik, J. (2026) · International Journal of Innovative Technologies in Social Science · doi:10.31435/ijitss.3(51).2026.5974
Management of Irritable Bowel Syndrome in the Patient with Ulcerative Colitis
Ginsburg, P. M., & Bayless, T. M. (2014) · Springer eBooks · doi:10.1007/978-1-4939-1677-1_40
- Authors
- Spiegel, B. M. R.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Spiegel, Brennan M.R.
- Venue
- Clinical Gastroenterology and Hepatology
- Publisher
- Elsevier BV
- Published
- 2011-06
- Volume
- 9
- Issue
- 6
- Pages
- 461-469
- ISSN
- 1542-3565 (ISSN-L)
- OpenAlex
- W2077093704
- Cited by
- 67
- References
- 96
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 1 · 2021: 3 · 2020: 1 · 2019: 5 · 2018: 2 · 2017: 3 · 2016: 5 · 2015: 6 · 2014: 19 · 2013: 3 · 2012: 8
- FWCI
- 1.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Clinical Gastroenterology and Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Health Professions › Pharmacy › Infant Health and Development
- Keywords
- irritable bowel syndrome, small intestinal bacterial overgrowth, lactulose breath test, small intestinal microbiota, causal hypotheses, evolutionary medicine, proton pump inhibitors, IBS treatment, number needed to treat, gut-brain axis, pathogenesis
- MeSH terms
- Bacteria, Humans, Intestine, Small, Irritable Bowel Syndrome
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