Small Intestinal Fungal Overgrowth

  • Askin Erdogan
  • Satish S. C. RaoEmail author
Neurogastroenterology and Motility Disorders of the Gastrointestinal Tract (S Rao, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Neurogastroenterology and Motility Disorders of the Gastrointestinal Tract


Small intestinal fungal overgrowth (SIFO) is characterized by the presence of excessive number of fungal organisms in the small intestine associated with gastrointestinal (GI) symptoms. Candidiasis is known to cause GI symptoms particularly in immunocompromised patients or those receiving steroids or antibiotics. However, only recently, there is emerging literature that an overgrowth of fungus in the small intestine of non-immunocompromised subjects may cause unexplained GI symptoms. Two recent studies showed that 26 % (24/94) and 25.3 % (38/150) of a series of patients with unexplained GI symptoms had SIFO. The most common symptoms observed in these patients were belching, bloating, indigestion, nausea, diarrhea, and gas. The underlying mechanism(s) that predisposes to SIFO is unclear but small intestinal dysmotility and use of proton pump inhibitors has been implicated. However, further studies are needed; both to confirm these observations and to examine the clinical relevance of fungal overgrowth, both in healthy subjects and in patients with otherwise unexplained GI symptoms. Importantly, whether eradication or its treatment leads to resolution of symptoms remains unclear; at present, a 2–3-week course of antifungal therapy is recommended and may be effective in improving symptoms, but evidence for eradication is lacking.


Small intestine Fungal overgrowth Symptoms Duodenal culture Diagnosis Treatment Review 



We acknowledge the technical and secretarial assistance of Ms. Helen Smith.

Compliance with Ethics Guidelines

Conflict of Interest

Askin Erdogan and Satish S.C. Rao declare that they have no conflict of interest.

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. Among cited articles where one of the authors of the current report were authors, local Institutional Review Board approval was obtained and maintained for studies where human (or animal) subjects research was performed.


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

  1. 1.
    Ruhnke M. Epidemiology of Candida albicans infections and role of non-Candida-albicans yeasts. Curr Drug Targets. 2006;7(4):495–504.PubMedCrossRefGoogle Scholar
  2. 2.
    Cimbaluk D, Scudiere J, Butsch J, Jakate S. Invasive candidal enterocolitis followed shortly by fatal cerebral hemorrhage in immunocompromised patients. J Clin Gastroenterol. 2005;39(9):795–7.PubMedCrossRefGoogle Scholar
  3. 3.
    Micames CG, Bentley R, Onken J. Clinical challenges and images in GI. Invasive candidal enterocolitis. Gastroenterology. 2007;133(2):391, 731. doi: 10.1053/j.gastro.2007.06.051.
  4. 4.
    Gupta TP, Ehrinpreis MN. Candida-associated diarrhea in hospitalized patients. Gastroenterology. 1990;98(3):780–5.PubMedGoogle Scholar
  5. 5.
    Greenspan D, Greenspan JS. HIV-related oral disease. Lancet. 1996;348(9029):729–33. doi: 10.1016/S0140-6736(96)02308-2.PubMedCrossRefGoogle Scholar
  6. 6.
    Gaitan-Cepeda LA, Sanchez-Vargas O, Castillo N. Prevalence of oral candidiasis in HIV/AIDS children in highly active antiretroviral therapy-era. A literature analysis. Int J STD AIDS. 2014. doi: 10.1177/0956462414548906.PubMedGoogle Scholar
  7. 7.
    Prescott RJ, Harris M, Banerjee SS. Fungal infections of the small and large intestine. J Clin Pathol. 1992;45(9):806–11.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Schulze J, Sonnenborn U. Yeasts in the gut: from commensals to infectious agents. Dtsch Arztebl Int. 2009;106(51–52):837–42. doi: 10.3238/arztebl.2009.0837.PubMedCentralPubMedGoogle Scholar
  9. 9.
    Cohen R, Roth FJ, Delgado E, Ahearn DG, Kalser MH. Fungal flora of the normal human small and large intestine. N Engl J Med. 1969;280(12):638–41. doi: 10.1056/NEJM196903202801204.PubMedCrossRefGoogle Scholar
  10. 10.••
    Jacobs C, Coss Adame E, Attaluri A, Valestin J, Rao SS. Dysmotility and proton pump inhibitor use are independent risk factors for small intestinal bacterial and/or fungal overgrowth. Aliment Pharmacol Ther. 2013;37(11):1103–11. doi: 10.1111/apt.12304. This is the first study investigating the prevalence of SIFO in patients with persistent GI symptoms, evaluating the symptoms of patients and showing that dysmotility and proton pomp use are independent risk factors for SIFO/SIBO. This study also showed that symptoms are poor predictors of SIFO and testing is essential.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Erdogan A, Lee Y, Sifuentes H, Rao SS. Small intestinal fungal overgrowth (SIFO): a cause of gastrointestinal symptoms. Gastroenterology. 2014;146(5):S-358.CrossRefGoogle Scholar
  12. 12.
    Yamashita K, Ohara M, Kojima T, Nishimura R, Ogawa T, Hino T, et al. Prevalence of drug-resistant opportunistic microorganisms in oral cavity after treatment for oral cancer. J Oral Sci. 2013;55(2):145–55.PubMedCrossRefGoogle Scholar
  13. 13.
    Kane JG, Chretien JH, Garagusi VF. Diarrhoea caused by Candida. Lancet. 1976;1(7955):335–6.PubMedCrossRefGoogle Scholar
  14. 14.
    Friedman M, Ramsay DB, Borum ML. An unusual case report of small bowel Candida overgrowth as a cause of diarrhea and review of the literature. Dig Dis Sci. 2007;52(3):679–80. doi: 10.1007/s10620-006-9604-4.PubMedCrossRefGoogle Scholar
  15. 15.
    Bodey GP. Candidiasis in cancer patients. Am J Med. 1984;77(4D):13–9.PubMedGoogle Scholar
  16. 16.
    Middleton SJ, Coley A, Hunter JO. The role of faecal Candida albicans in the pathogenesis of food-intolerant irritable bowel syndrome. Postgrad Med J. 1992;68(800):453–4.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Forbes D, Ee L, Camer-Pesci P, Ward PB. Faecal candida and diarrhoea. Arch Dis Child. 2001;84(4):328–31.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Florescu DF, Islam KM, Grant W, Mercer DF, Langnas A, Botha J, et al. Incidence and outcome of fungal infections in pediatric small bowel transplant recipients. Transpl Infect Dis Off J Transplant Soc. 2010;12(6):497–504. doi: 10.1111/j.1399-3062.2010.00542.x.CrossRefGoogle Scholar
  19. 19.
    Hube B. From commensal to pathogen: stage- and tissue-specific gene expression of Candida albicans. Curr Opin Microbiol. 2004;7(4):336–41. doi: 10.1016/j.mib.2004.06.003.PubMedCrossRefGoogle Scholar
  20. 20.
    Netea MG, Brown GD, Kullberg BJ, Gow NA. An integrated model of the recognition of Candida albicans by the innate immune system. Nat Rev Microbiol. 2008;6(1):67–78. doi: 10.1038/nrmicro1815.PubMedCrossRefGoogle Scholar
  21. 21.
    Blanco JL, Garcia ME. Immune response to fungal infections. Vet Immunol Immunopathol. 2008;125(1–2):47–70. doi: 10.1016/j.vetimm.2008.04.020.PubMedCrossRefGoogle Scholar
  22. 22.
    Vilanova M, Correia A. Host defense mechanisms in invasive candidiasis originating in the GI tract. Expert Rev Anti-Infect Ther. 2008;6(4):441–5. doi: 10.1586/14787210.6.4.441.PubMedCrossRefGoogle Scholar
  23. 23.
    Fidel Jr PL. History and update on host defense against vaginal candidiasis. Am J Reprod Immunol. 2007;57(1):2–12. doi: 10.1111/j.1600-0897.2006.00450.x.PubMedCrossRefGoogle Scholar
  24. 24.
    Polonelli L, Casadevall A, Han Y, Bernardis F, Kirkland TN, Matthews RC, et al. The efficacy of acquired humoral and cellular immunity in the prevention and therapy of experimental fungal infections. Med Mycol. 2000;38 Suppl 1:281–92.PubMedCrossRefGoogle Scholar
  25. 25.
    Traynor TR, Huffnagle GB. Role of chemokines in fungal infections. Med Mycol. 2001;39(1):41–50.PubMedCrossRefGoogle Scholar
  26. 26.••
    Iliev ID, Funari VA, Taylor KD, Nguyen Q, Reyes CN, Strom SP, et al. Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis. Science. 2012;336(6086):1314–7. doi: 10.1126/science.1221789. This study found that fungi in colonic tissue are abundant, closely located with commensal bacteria, and commensal fungi are recognized by Dectin-1. The authors also showed that Dectin-1 deficiency leads to increased susceptibility to colitis. Although 7/20 of most common fungi were found in mice food, this only represented for 1.5 % of fungi in the intestine indicating that those species mostly found in the gut are native to the gut. Furthermore, treatment of colitis with fluconazole reduced weight loss and caused milder histological disease findings indicating the effect of fungi on gut health.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Wang ZK, Yang YS, Stefka AT, Sun G, Peng LH. Review article: fungal microbiota and digestive diseases. Aliment Pharmacol Ther. 2014;39(8):751–66. doi: 10.1111/apt.12665.PubMedCrossRefGoogle Scholar
  28. 28.
    Shirtliff ME, Peters BM, Jabra-Rizk MA. Cross-kingdom interactions: Candida albicans and bacteria. FEMS Microbiol Lett. 2009;299(1):1–8. doi: 10.1111/j.1574-6968.2009.01668.x.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Frey-Klett P, Burlinson P, Deveau A, Barret M, Tarkka M, Sarniguet A. Bacterial-fungal interactions: hyphens between agricultural, clinical, environmental, and food microbiologists. Microbiol Mol Biol Rev. 2011;75(4):583–609. doi: 10.1128/MMBR. 00020-11.PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Fitzsimmons N, Berry DR. Inhibition of Candida albicans by Lactobacillus acidophilus: evidence for the involvement of a peroxidase system. Microbios. 1994;80(323):125–33.PubMedGoogle Scholar
  31. 31.
    Calderone RA, Fonzi WA. Virulence factors of Candida albicans. Trends Microbiol. 2001;9(7):327–35.PubMedCrossRefGoogle Scholar
  32. 32.
    Franke A, Balschun T, Sina C, Ellinghaus D, Hasler R, Mayr G, et al. Genome-wide association study for ulcerative colitis identifies risk loci at 7q22 and 22q13 (IL17REL). Nat Genet. 2010;42(4):292–4. doi: 10.1038/ng.553.PubMedCrossRefGoogle Scholar
  33. 33.
    McGovern DP, Gardet A, Torkvist L, Goyette P, Essers J, Taylor KD, et al. Genome-wide association identifies multiple ulcerative colitis susceptibility loci. Nat Genet. 2010;42(4):332–7. doi: 10.1038/ng.549.PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Seow CH, Stempak JM, Xu W, Lan H, Griffiths AM, Greenberg GR, et al. Novel anti-glycan antibodies related to inflammatory bowel disease diagnosis and phenotype. Am J Gastroenterol. 2009;104(6):1426–34. doi: 10.1038/ajg.2009.79.PubMedCrossRefGoogle Scholar
  35. 35.
    Joossens S, Reinisch W, Vermeire S, Sendid B, Poulain D, Peeters M, et al. The value of serologic markers in indeterminate colitis: a prospective follow-up study. Gastroenterology. 2002;122(5):1242–7.PubMedCrossRefGoogle Scholar
  36. 36.
    Van der Graaf CA, Netea MG, Morre SA, Den Heijer M, Verweij PE, Van der Meer JW, et al. Toll-like receptor 4 Asp299Gly/Thr399Ile polymorphisms are a risk factor for Candida bloodstream infection. Eur Cytokine Netw. 2006;17(1):29–34.PubMedGoogle Scholar
  37. 37.
    Devlin SM, Yang H, Ippoliti A, Taylor KD, Landers CJ, Su X, et al. NOD2 variants and antibody response to microbial antigens in Crohn’s disease patients and their unaffected relatives. Gastroenterology. 2007;132(2):576–86. doi: 10.1053/j.gastro.2006.11.013.PubMedCrossRefGoogle Scholar
  38. 38.
    Rubinstein E, Mark Z, Haspel J, Ben-Ari G, Dreznik Z, Mirelman D, et al. Antibacterial activity of the pancreatic fluid. Gastroenterology. 1985;88(4):927–32.PubMedGoogle Scholar
  39. 39.••
    Gong YB, Zheng JL, Jin B, Zhuo DX, Huang ZQ, Qi H, et al. Particular Candida albicans strains in the digestive tract of dyspeptic patients, identified by multilocus sequence typing. PLoS ONE. 2012;7(4):e35311. doi: 10.1371/journal.pone.0035311. This study shows that Candida albicans colonizes oral flora as well as gastric flora of dyspeptic patients; overall C. albicans was isolated from 97.8 % of the Candida-positive subjects from oral/gastric samples in the dyspeptic group, but from only 56.3 % in the healthy group (P, 0.001). This study suggests that Candida albicans can survive in gastric acidity.PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.•
    Banerjee P, Kaur R, Uppal B. Study of fungal isolates in patients with chronic diarrhea at a tertiary care hospital in north India. J Mycol Med. 2013;23(1):21–6. doi: 10.1016/j.mycmed.2012.12.002. This study was carried out in patients suffering from chronic diarrhea and aimed to find the rate of isolation of yeast from stool and also antifungal susceptibility of opportunistic pathogens. Of total, 26.7 % of stool specimens grew fungal organisms and most were found to be sensitive to antifungal agents including fluconazole. This study shows that opportunistic yeast may cause symptoms like chronic diarrhea.PubMedCrossRefGoogle Scholar
  41. 41.
    Rex JH, Rinaldi MG, Pfaller MA. Resistance of Candida species to fluconazole. Antimicrob Agents Chemother. 1995;39(1):1–8.PubMedCentralPubMedCrossRefGoogle Scholar
  42. 42.
    Pfaller MA, Jones RN, Messer SA, Edmond MB, Wenzel RP. National surveillance of nosocomial blood stream infection due to species of Candida other than Candida albicans: frequency of occurrence and antifungal susceptibility in the SCOPE Program. SCOPE Participant Group. Surveillance and Control of Pathogens of Epidemiologic. Diagn Microbiol Infect Dis. 1998;30(2):121–9.PubMedCrossRefGoogle Scholar
  43. 43.
    Zonios DI, Bennett JE. Update on azole antifungals. Semin Respir Crit Care Med. 2008;29(2):198–210. doi: 10.1055/s-2008-1063858.PubMedCrossRefGoogle Scholar
  44. 44.
    Phillips P, Shafran S, Garber G, Rotstein C, Smaill F, Fong I, et al. Multicenter randomized trial of fluconazole versus amphotericin B for treatment of candidemia in non-neutropenic patients. Canadian Candidemia Study Group. Eur J Clin Microbiol Infect Dis Off Publ Eur Soc Clin Microbiol. 1997;16(5):337–45.CrossRefGoogle Scholar
  45. 45.
    Rex JH, Pappas PG, Karchmer AW, Sobel J, Edwards JE, Hadley S, et al. A randomized and blinded multicenter trial of high-dose fluconazole plus placebo versus fluconazole plus amphotericin B as therapy for candidemia and its consequences in nonneutropenic subjects. Clin Infect Dis Off Publ Infect Dis Soc Am. 2003;36(10):1221–8. doi: 10.1086/374850.CrossRefGoogle Scholar
  46. 46.
    Jiang L, Yong X, Li R, Peng Y, Liu W, Qin Q, et al. Dynamic analysis of oral Candida carriage, distribution, and antifungal susceptibility in HIV-infected patients during the first year of highly active antiretroviral therapy in Guangxi, China. J Oral Pathol Med Off Publ Int Assoc Oral Pathol Am Acad Oral Pathol. 2014. doi: 10.1111/jop.12192.Google Scholar
  47. 47.
    Pfaller MA, Jones RN, Doern GV, Fluit AC, Verhoef J, Sader HS, et al. International surveillance of blood stream infections due to Candida species in the European SENTRY Program: species distribution and antifungal susceptibility including the investigational triazole and echinocandin agents. SENTRY Participant Group (Europe). Diagn Microbiol Infect Dis. 1999;35(1):19–25.PubMedCrossRefGoogle Scholar
  48. 48.
    Denning DW. Echinocandin antifungal drugs. Lancet. 2003;362(9390):1142–51. doi: 10.1016/S0140-6736(03)14472-8.PubMedCrossRefGoogle Scholar
  49. 49.
    Bennett JE. Echinocandins for candidemia in adults without neutropenia. N Engl J Med. 2006;355(11):1154–9. doi: 10.1056/NEJMct060052.PubMedCrossRefGoogle Scholar
  50. 50.
    Johansen HK, Gotzsche PC. Amphotericin B lipid soluble formulations versus amphotericin B in cancer patients with neutropenia. Cochrane Database Syst Rev. 2014;9, CD000969. doi: 10.1002/14651858.CD000969.pub2.PubMedGoogle Scholar
  51. 51.
    Gotzsche PC, Johansen HK. Nystatin prophylaxis and treatment in severely immunodepressed patients. Cochrane Database Syst Rev. 2014;9, CD002033. doi: 10.1002/14651858.CD002033.pub2.PubMedGoogle Scholar
  52. 52.
    Chandrasekar P. Management of invasive fungal infections: a role for polyenes. J Antimicrob Chemother. 2011;66(3):457–65. doi: 10.1093/jac/dkq479.PubMedCrossRefGoogle Scholar
  53. 53.
    Maroszynska M, Kunicka-Styczynska A, Rajkowska K, Maroszynska I. Antibiotics sensitivity of Candida clinical and food-borne isolates. Acta Biochim Pol. 2013;60(4):719–24.PubMedGoogle Scholar
  54. 54.••
    Pappas PG, Kauffman CA, Andes D, Benjamin Jr DK, Calandra TF, Edwards Jr JE, et al. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis Off Publ Infect Dis Soc Am. 2009;48(5):503–35. doi: 10.1086/596757. This infectious disease society guideline provides comprehensive information on the various drugs, their mechanism of action and profile and indication for treatment of candidiasis.CrossRefGoogle Scholar

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© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Section of Gastroenterology and HepatologyGeorgia Regents UniversityAugustaUSA
  2. 2.Department of Medicine, Section of Gastroenterology and Hepatology, Medical College of GeorgiaGeorgia Regents UniversityAugustaUSA

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