Advertisement

The Spectrum of Small Intestinal Bacterial Overgrowth (SIBO)

  • Eamonn M. M. QuigleyEmail author
Small Intestine (D Sachar, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Small Intestine

Abstract

Purpose of Review

To critically review recent (past 3 years) literature on the definition, diagnosis, and management of small intestinal bacterial overgrowth (SIBO).

Recent Findings

While various series continue to illustrate the occurrence of SIBO in disease states where well-known risk factors for its occurrence are present (hypochlorhydria, disorders of intestinal structure or motor function, pancreatic insufficiency, and chronic liver disease, for example), the current challenge is in defining the limits of SIBO. Is SIBO truly common among those with “functional” gastrointestinal symptoms where there is no evidence of maldigestion or malabsorption; the original hallmarks of SIBO? Our attempts to address this question continue to be hampered by the limitations of our diagnostic tool kit. There is hope—the application of modern molecular techniques to the study of the small intestinal microbiome, together with some innovative sampling techniques, such as real-time intestinal gas sampling, may soon allow us to truly define the spectrum of SIBO.

Summary

SIBO, once removed from its original confines as a cause of malabsorption syndrome, has proven to be an elusive and moving target. Only the most rigorous studies employing validated methodologies will finally corral this mysterious entity.

Keywords

Small intestinal bacterial overgrowth Microbiome Breath testing Hydrogen methane Rifaximin 

Notes

Funding

This study is supported, in part, by a bequest from the Hughes-Sterling Foundation.

Compliance with Ethical Standards

Conflict of Interest

Eamonn M M Quigley reports consultancies with and/or research support from 4D Pharma, Alimentary Health, Allergan, Axon Pharma, Biocodex, Glycyx, Ironwood, Pharmasierra, Salix, Shire, Takeda, Vibrant, and Zeeland.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Quigley EMM. Small intestinal bacterial overgrowth: what it is and what it is not. Curr Opin Gastroenterol. 2014;30:141–6.CrossRefGoogle Scholar
  2. 2.
    Quigley EMM. Bacterial overgrowth. In: Camilleri M, Fitz JG, Kalloo AN, Podolsky DK, Shanahan F, Wang TC, editors. Yamada’s textbook of gastroenterology. 6th ed. Wiley: Chichester; 2016. p. 1294–304.Google Scholar
  3. 3.
    Shanahan ER, Zhong L, Talley NJ, Morrison M, Holtmann G. Characterisation of the gastrointestinal mucosa-associated microbiota: a novel technique to prevent cross-contamination during endoscopic procedures. Aliment Pharmacol Ther. 2016;43:1186–96.CrossRefGoogle Scholar
  4. 4.
    Di Stefano M, Quigley EMM. The diagnosis of small intestinal bacterial overgrowth: two steps forward, one step backwards? Neurogastroenterol Motil. 2018;30:e13494.CrossRefGoogle Scholar
  5. 5.
    • Rezaie A, Buresi M, Lembo A, Lin H, McCallum R, Rao S, et al. Hydrogen and methane-based breath testing in gastrointestinal disorders: the North American consensus. Am J Gastroenterol. 2017;112:775–8 A detailed examination of current criteria for the diagnosis of SIBO together with consensus-based recommendations for the performance and interpretation of breath tests. CrossRefGoogle Scholar
  6. 6.
    Yu D, Cheesman F, Vanner S. Combined oro-cecal scintigraphy and lactulose hydrogen breath testing demonstrate that breath testing detects oro-cecal transit, not small intestinal bacterial overgrowth in patients with IBS. Gut. 2011;60:334–40.CrossRefGoogle Scholar
  7. 7.
    Paterson W, Camilleri M, Simren M, Boeckxstaens G, Vanner SJ. Breath testing consensus guidelines for SIBO: RES IPSA LOCQUITOR. Am J Gastroenterol. 2017;112:1888–9.CrossRefGoogle Scholar
  8. 8.
    Rezaie A, Buresi M, Rao S. Response to Paterson et al. Am J Gastroenterol. 2017;112:1889–92.CrossRefGoogle Scholar
  9. 9.
    Lin EC, Massey BT. Scintigraphy demonstrates high rate of false positive results from glucose breath tests for small bowel bacterial overgrowth. Clin Gastroenterol Hepatol. 2016;124:203–8.CrossRefGoogle Scholar
  10. 10.
    • Sundin O, Mendoza-Ladd A, Morales E, Fagan BM, Zeng M, Diaz-Arevalo D, et al. Does glucose-based hydrogen and methane breath test detect bacterial overgrowth in the jejunum? Neurogastroenterol Motil. 2018;30:e13350 Questions the validity of glucose- based breath tests.CrossRefGoogle Scholar
  11. 11.
    Quigley EMM. Gut microbiome as a clinical tool in gastrointestinal disease management: are we there yet? Nat Rev Gastroenterol Hepatol. 2017;14:315–20.CrossRefGoogle Scholar
  12. 12.
    • Berean KJ, Ha N, Ou JZ, Chrimes AF, Grando D, Yao CK, et al. The safety and sensitivity of a telemetric capsule to monitor gastrointestinal hydrogen production in vivo in healthy subjects: a pilot trial comparison to concurrent breath analysis. Aliment Pharmacol Ther. 2018;48:646–54 Pilot data on a very exciting novel technology which provides real time data on intestinal gas production. CrossRefGoogle Scholar
  13. 13.
    Kundu P, Blacher E, Elinav E, Petterson S. Our gut microbiome: the evolving inner self. Cell. 2017;171:1481–93.CrossRefGoogle Scholar
  14. 14.
    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.CrossRefGoogle Scholar
  15. 15.
    Brechmann T, Sperlbaum A, Schmiegel W. Levothyroxine therapy and impaired clearance are the strongest contributors to small intestinal bacterial overgrowth: results of a retrospective cohort study. World J Gastroenterol. 2017;23:842–52.CrossRefGoogle Scholar
  16. 16.
    Robey BS, Peery AF, Dellon ES. Small bowel diverticulosis and jejunal perforation in Marfan syndrome. ACG Case Rep J. 2018;5:e5.CrossRefGoogle Scholar
  17. 17.
    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. 2018;53:27–36.CrossRefGoogle Scholar
  18. 18.
    Chander Roland B, Mullin GE, Passi M, Zheng X, Salem A, Yolken R, et al. A prospective evaluation of ileocecal valve dysfunction and intestinal motility derangements in small intestinal bacterial overgrowth. Dig Dis Sci. 2017;62:3525–35.CrossRefGoogle Scholar
  19. 19.
    Roland BC, Ciarleglio MM, Clarke JO, Semler JR, Tomakin E, Mullin GE, et al. Small intestinal transit time is delayed in small intestinal bacterial overgrowth. J Clin Gastroenterol. 2015;49:571–6.CrossRefGoogle Scholar
  20. 20.
    Tauber M, Avouac J, Benahmed A, Barbot L, Coustet B, Kahan A, et al. Prevalence and predictors of small intestinal bacterial overgrowth in systemic sclerosis patients with gastrointestinal symptoms. Clin Exp Rheumatol. 2014;32(6 Suppl 86):S-82-7.PubMedGoogle Scholar
  21. 21.
    Pittman N, Rawn SM, Wang M, Masetto A, Beattie KA, Larche M. Treatment of small intestinal bacterial overgrowth in systemic sclerosis: a systematic review. Rheumatology (Oxford). 2018;57:1802–11.CrossRefGoogle Scholar
  22. 22.
    Deloose E, Tack J. Redefining the functional roles of the gastrointestinal migrating motor complex and motilin in small bacterial overgrowth and hunger signaling. Am J Physiol Gastrointest Liver Physiol. 2016;310:G228–33.CrossRefGoogle Scholar
  23. 23.
    Suri J, Kataria R, Malik Z, Parkman HP, Schey R. Elevated methane levels in small intestinal bacterial overgrowth suggests delayed small bowel and colonic transit. Medicine (Baltimore). 2018;97:e10554.CrossRefGoogle Scholar
  24. 24.
    Robinson-Papp J, Nmashie A, Pedowitz E, Benn EKT, George MC, Sharma S, et al. Vagal dysfunction and small intestinal bacterial overgrowth: novel pathways to chronic inflammation in HIV. AIDS. 2018;32:1147–56.CrossRefGoogle Scholar
  25. 25.
    Greco A, Caviglia GP, Brignolo P, Ribaldone DG, Reggiani S, Sguazzini C, et al. Glucose breath test and Crohn's disease: diagnosis of small intestinal bacterial overgrowth and evaluation of therapeutic response. Scand J Gastroenterol. 2015;50:1376–81.CrossRefGoogle Scholar
  26. 26.
    Ricci JERJ, Chebli LA, Ribeiro TCDR, Castro ACS, Gaburri PD, Pace FHDL, et al. Small-intestinal bacterial overgrowth is associated with concurrent intestinal inflammation but not with systemic inflammation in Crohn’s disease patients. J Clin Gastroenterol. 2018;52:530–6.Google Scholar
  27. 27.
    • Cohen-Mekelburg S, Tafesh Z, Coburn E, Weg R, Malik N, Webb C, Hammad H, Scherl E, Bosworth BP. Testing and treating small intestinal bacterial overgrowth reduces symptoms in patients with inflammatory bowel disease. Dig Dis Sci. 2018. Emphasizes the need to consider SIBO in the symptomatic IBD patient. Google Scholar
  28. 28.
    Losurdo G, Marra A, Shahini E, Girardi B, Giorgio F, Amoruso A, et al. Small intestinal bacterial overgrowth and celiac disease: a systematic review with pooled-data analysis. Neurogastroenterol Motil. 2017;29.Google Scholar
  29. 29.
    • Capurso G, Signoretti M, Archibugi L, Stigliano S, Delle FG. Systematic review and meta-analysis: small intestinal bacterial overgrowth in chronic pancreatitis. United European Gastroenterol J. 2016;4:697–705 Describes the prevalence of and risk factors for SIBO in chronic pancreatitis. CrossRefGoogle Scholar
  30. 30.
    Ní Chonchubhair HM, Bashir Y, Dobson M, Ryan BM, Duggan SN, Conlon KC. The prevalence of small intestinal bacterial overgrowth in non-surgical patients with chronic pancreatitis and pancreatic exocrine insufficiency (PEI). Pancreatology. 2018;18:379–85.CrossRefGoogle Scholar
  31. 31.
    Therrien A, Bouchard S, Sidani S, Bouin M. Prevalence of small intestinal bacterial overgrowth among chronic pancreatitis patients: a case-control study. Can J Gastroenterol Hepatol. 2016;2016:7424831.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Kim DB, Paik CN, Sung HJ, Chung WC, Lee KM, Yang JM, et al. Breath hydrogen and methane are associated with intestinal symptoms in patients with chronic pancreatitis. Pancreatology. 2015;15:514–8.CrossRefGoogle Scholar
  33. 33.
    Zhang M, Zhu HM, He F, Li BY, Li XC. Association between acute pancreatitis and small intestinal bacterial overgrowth assessed by hydrogen breath test. World J Gastroenterol. 2017;23:8591–6.CrossRefGoogle Scholar
  34. 34.
    • Shah A, Shanahan E, Macdonald GA, Fletcher L, Ghasemi P, Morrison M, et al. Systematic review and meta-analysis: prevalence of small intestinal bacterial overgrowth in chronic liver disease. Semin Liver Dis. 2017;37:388–400 Reaffirms, within the limits of diagnostic methodology, the association between SIBO and chronic liver disease. CrossRefGoogle Scholar
  35. 35.
    Zhang Y, Feng Y, Cao B, Tian Q. The effect of small intestinal bacterial overgrowth on minimal hepatic encephalopathy in patients with cirrhosis. Arch Med Sci. 2016;12:592–6.CrossRefGoogle Scholar
  36. 36.
    Victor DW 3rd, Quigley EM. The microbiome and the liver: the basics. Semin Liver Dis. 2016;36:299–305.CrossRefGoogle Scholar
  37. 37.
    Quigley EM, Abu-Shanab A, Murphy EF, Stanton C, Monsour HP Jr. The metabolic role of the microbiome: implications for NAFLD and the metabolic syndrome. Semin Liver Dis. 2016;36:312–6.CrossRefGoogle Scholar
  38. 38.
    Fialho A, Fialho A, Thota P, McCullough A, Shen B. Higher visceral to subcutaneous fat ratio is associated with small intestinal bacterial overgrowth. Nutr Metab Cardiovasc Dis. 2016;26:773–7.CrossRefGoogle Scholar
  39. 39.
    Sabate JM, Coupaye M, Ledoux S, Castel B, Msika S, Coffin B, et al. Consequences of small intestinal bacterial overgrowth in obese patients before and after bariatric surgery. Obes Surg. 2017;27:599–605.CrossRefGoogle Scholar
  40. 40.
    Roland BC, Lee D, Miller LS, Vegesna A, Yolken R, Severance E, et al. Obesity increases the risk of small intestinal bacterial overgrowth (SIBO). Neurogastroenterol Motil. 2018;30.Google Scholar
  41. 41.
    Belei O, Olariu L, Dobrescu A, Marcovici T, Marginean O. The relationship between non-alcoholic fatty liver disease and small intestinal bacterial overgrowth among overweight and obese children and adolescents. J Pediatr Endocrinol Metab. 2017;30:1161–8.CrossRefGoogle Scholar
  42. 42.
    Rana SV, Malik A, Bhadada SK, Sachdeva N, Morya RK, Sharma G. Malabsorption, orocecal transit time and small intestinal bacterial overgrowth in type 2 diabetic patients: a connection. Indian J Clin Biochem. 2017;32:84–9.CrossRefGoogle Scholar
  43. 43.
    Ghoshal UC, Baba CS, Ghoshal U, Alexander G, Misra A, Saraswat VA, et al. Low-grade small intestinal bacterial overgrowth is common in patients with non-alcoholic steatohepatitis on quantitative jejunal aspirate culture. Indian J Gastroenterol. 2017;36:390–9.CrossRefGoogle Scholar
  44. 44.
    Kapil S, Duseja A, Sharma BK, Singla B, Chakraborti A, Das A, et al. Small intestinal bacterial overgrowth and toll-like receptor signaling in patients with non-alcoholic fatty liver disease. J Gastroenterol Hepatol. 2016;31:213–21.CrossRefGoogle Scholar
  45. 45.
    Jung SE, Joo NS, Han KS, Kim KN. Obesity is inversely related to hydrogen-producing small intestinal bacterial overgrowth in non-constipation irritable bowel syndrome. J Korean Med Sci. 2017;32:948–53.CrossRefGoogle Scholar
  46. 46.
    Fialho A, Fialho A, Kochhar G, Schenone AL, Thota P, McCullough AJ, et al. Association between small intestinal bacterial overgrowth by glucose breath test and coronary artery disease. Dig Dis Sci. 2018;63:412–21.CrossRefGoogle Scholar
  47. 47.
    Ponziani FR, Pompili M, Di Stasio E, Zocco MA, Gasbarrini A, Flore R. Subclinical atherosclerosis is linked to small intestinal bacterial overgrowth via vitamin K2-dependent mechanisms. World J Gastroenterol. 2017 Feb;23:1241–9.CrossRefGoogle Scholar
  48. 48.
    Quigley EMM. Microbiota-brain-gut axis and neurodegenerative diseases. Curr Neurol Neurosci Rep. 2017;17:94.CrossRefGoogle Scholar
  49. 49.
    Tan AH, Mahadeva S, Thalha AM, Gibson PR, Kiew CK, Yeat CM, et al. Small intestinal bacterial overgrowth in Parkinson’s disease. Parkinsonism Relat Disord. 2014;20:535–40.CrossRefGoogle Scholar
  50. 50.
    Niu XL, Liu L, Song ZX, Li Q, Wang ZH, Zhang JL, et al. Prevalence of small intestinal bacterial overgrowth in Chinese patients with Parkinson’s disease. J Neural Transm (Vienna). 2016;123:1381–6.CrossRefGoogle Scholar
  51. 51.
    Vizcarra JA, Wilson-Perez HE, Fasano A, Espay AJ. Small intestinal bacterial overgrowth in Parkinson’s disease: tribulations of a trial. Parkinsonism Relat Disord. 2018;54:110–2.CrossRefGoogle Scholar
  52. 52.
    Zhang Y, Liu G, Duan Y, Han X, Dong H, Geng J. Prevalence of small intestinal bacterial overgrowth in multiple sclerosis: a case-control study from China. J Neuroimmunol. 2016;301:83–7.CrossRefGoogle Scholar
  53. 53.
    • Donowitz JR, Haque R, Kirkpatrick BD, Alam M, Lu M, Kabir M, et al. Small intestine bacterial overgrowth and environmental enteropathy in Bangladeshi children. MBio. 2016;7:e02102–15 Describes the prevalence and nutritional implications of SIBO in an at-risk population. CrossRefGoogle Scholar
  54. 54.
    Fialho A, Fialho A, Schenone A, Thota P, McCullough A, Shen B. Association between small intestinal bacterial overgrowth and deep vein thrombosis. Gastroenterol Rep (Oxf). 2016;4:299–303.Google Scholar
  55. 55.
    Enko D, Kriegshäuser G. Functional 13C-urea and glucose hydrogen/methane breath tests reveal significant association of small intestinal bacterial overgrowth in individuals with active Helicobacter pylori infection. Clin Biochem. 2017;50:46–9.CrossRefGoogle Scholar
  56. 56.
    Verrecchia E, Sicignano LL, La Regina M, Nucera G, Patisso I, Cerrito L, et al. Small intestinal bacterial overgrowth affects the responsiveness to colchicine in familial Mediterranean fever. Mediat Inflamm. 2017;2017:7461426.CrossRefGoogle Scholar
  57. 57.
    Kim DB, Paik CN, Song DS, Kim YJ, Lee JM. The characteristics of small intestinal bacterial overgrowth in patients with gallstone diseases. J Gastroenterol Hepatol. 2018;33:1477–84.CrossRefGoogle Scholar
  58. 58.
    Deng L, Liu Y, Zhang D, Li Y, Xu L. Prevalence and treatment of small intestinal bacterial overgrowth in postoperative patients with colorectal cancer. Mol Clin Oncol. 2016;4:883–7.CrossRefGoogle Scholar
  59. 59.
    Rao SSC, Tan G, Abdulla H, Yu S, Larion S, Leelasinjaroen P. Does colectomy predispose to small intestinal bacterial (SIBO) and fungal overgrowth (SIFO)? Clin Transl Gastroenterol. 2018;9:146.PubMedPubMedCentralGoogle Scholar
  60. 60.
    Jung HJ, Paik CN, Chung WC, Lee KM, Yang JM, Choi MG. Small intestinal bacterial overgrowth diagnosed by glucose hydrogen breath test in post-cholecystectomy patients. J Neurogastroenterol Motil. 2015;21:545–51.CrossRefGoogle Scholar
  61. 61.
    • Chen B, Kim JJ, Zhang Y, Du L, Dai N. Prevalence and predictors of small intestinal bacterial overgrowth in irritable bowel syndrome: a systematic review and meta-analysis. J Gastroenterol. 2018.  https://doi.org/10.1007/s00535-018-1476-9. The latest systematic review on this controversial topic.
  62. 62.
    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 Jul;16:67.CrossRefGoogle Scholar
  63. 63.
    Chu H, Fox M, Zheng X, Deng Y, Long Y, Huang Z, et al. Small intestinal bacterial overgrowth in patients with irritable bowel syndrome: clinical characteristics, psychological factors, and peripheral cytokines. Gastroenterol Res Pract. 2016;2016:3230859.PubMedPubMedCentralGoogle Scholar
  64. 64.
    Long SK, Di Palma JA. Does carbohydrate challenge testing predict clinical response in small intestinal bacterial overgrowth? South Med J. 2016;109:296–9.CrossRefGoogle Scholar
  65. 65.
    Ghoshal UC, Srivastava D, Misra A, Ghoshal U. A proof-of-concept study showing antibiotics to be more effective in irritable bowel syndrome with than without small-intestinal bacterial overgrowth: a randomized, double-blind, placebo-controlled trial. Eur J Gastroenterol Hepatol. 2016;28:281–9.CrossRefGoogle Scholar
  66. 66.
    Acosta A, Camilleri M, Shin A, Linker Nord S, O'Neill J, Gray AV, et al. Effects of rifaximin on transit, permeability, fecal microbiome, and organic acid excretion in irritable bowel syndrome. Clin Transl Gastroenterol. 2016;7:e173.CrossRefGoogle Scholar
  67. 67.
    • Ghoshal UC, Gwee KA. Post-infectious IBS, tropical sprue and small intestinal bacterial overgrowth: the missing link. Nat Rev Gastroenterol Hepatol. 2017;14:435–41 Interesting discussion on the relationships between these disorders, proposing SIBO as the common factor. CrossRefGoogle Scholar
  68. 68.
    • Aziz I, Törnblom H, Simrén M. Small intestinal bacterial overgrowth as a cause for irritable bowel syndrome: guilty or not guilty? Curr Opin Gastroenterol. 2017;33:196–202 A carefully argued critical review of the status of the SIBO-IBS relationship. CrossRefGoogle Scholar
  69. 69.
    Yao J, Chang L, Yuan L, Duan Z. Nutrition status and small intestinal bacterial overgrowth in patients with virus-related cirrhosis. Asia Pac J Clin Nutr. 2016;25:283–91.PubMedGoogle Scholar
  70. 70.
    Oliveira RB, Martinelli ALC, Troncon LEA, Elias J Jr. Small intestinal bacterial overgrowth (SIBO) and vitamin K-responsive coagulopathy: a previously unrecorded association. BMJ Case Rep. 2018.  https://doi.org/10.1136/bcr-2017-223531.
  71. 71.
    Cheng X, Zhang L, Xie NC, Xu HL, Lian YJ. Association between small-intestinal bacterial overgrowth and deep vein thrombosis in patients with spinal cord injuries. J Thromb Haemost. 2017;15:304–11.CrossRefGoogle Scholar
  72. 72.
    McIntosh S, Medjoub K, Deans K, Sexton S. Hyperammonaemic encephalopathy following an uncomplicated surgery. BMJ Case Rep 2017.  https://doi.org/10.1136/bcr-2017-221458.
  73. 73.
    Gatta L, Scarpignato C. Systematic review with meta-analysis: rifaximin is effective and safe for the treatment of small intestine bacterial overgrowth. Aliment Pharmacol Ther. 2017;45:604–16.CrossRefGoogle Scholar
  74. 74.
    Zhong C, Qu C, Wang B, Liang S, Zeng B. Probiotics for preventing and treating small intestinal bacterial overgrowth: a meta-analysis and systematic review of current evidence. J Clin Gastroenterol. 2017;51:300–11.CrossRefGoogle Scholar
  75. 75.
    • Adike A, DiBaise JK. Small intestinal bacterial overgrowth: nutritional implications, diagnosis, and management. Gastroenterol Clin N Am. 2018;47:193–208 An up-to-date review of SIBO management. CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Lynda K and David M Underwood Center for Digestive Disorders, Division of Gastroenterology and Hepatology, Houston Methodist HospitalWeill Cornell Medical CollegeHoustonUSA
  2. 2.Houston Methodist Gastroenterology AssociatesHoustonUSA

Personalised recommendations