Gastrointestinal Colonization of Fungi

Abstract

The human gastrointestinal tract is colonized with trillions of commensal microbes, and disturbances in the equilibrium of the gut microbiota have now been shown to be associated with a number of human diseases. Fungi, particularly Candida spp., are normal, harmless residents of the human gut, but in certain instances can cause invasive infections and inflammatory disorders. This paper will review the fungal diversity in the human gut, host and fungal factors that regulate GI colonization, and how these factors play into the pathogenesis of human disease.

This is a preview of subscription content, access via your institution.

References

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

  1. 1.

    Backhed F, Ley RE, Sonnenburg JL, et al. Host-bacterial mutualism in the human intestine. Science. 2005;307:1915–20.

    PubMed  Article  Google Scholar 

  2. 2.

    Round JL, Mazmanian SK. The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol. 2009;9:313–23.

    PubMed  Article  CAS  Google Scholar 

  3. 3.

    Marchesi JR. Prokaryotic and eukaryotic diversity of the human gut. Adv Appl Microbiol. 2010;72:43–62.

    PubMed  Article  Google Scholar 

  4. 4.

    Nam YD, Chang HW, Kim KH, et al. Bacterial, archaeal, and eukaryal diversity in the intestines of Korean people. J Microbiol. 2008;46:491–501.

    PubMed  Article  CAS  Google Scholar 

  5. 5.

    Ott SJ, Kuhbacher T, Musfeldt M, et al. Fungi and inflammatory bowel diseases: alterations of composition and diversity. Scand J Gastroenterol. 2008;43:831–41.

    PubMed  Article  CAS  Google Scholar 

  6. 6.

    Scanlan PD, Marchesi JR. Micro-eukaryotic diversity of the human distal gut microbiota: qualitative assessment using culture-dependent and -independent analysis of faeces. ISME J. 2008;2:1183–93.

    PubMed  Article  CAS  Google Scholar 

  7. 7.

    Church C, Neill A, Schotthoefer AM. Intestinal infections in humans in the Rocky Mountain region, United States. J Parasitol. 2010;96:194–6.

    PubMed  Article  Google Scholar 

  8. 8.

    Macura AB, Witalis J. Fungi isolated from the stool in patients with gastrointestinal disorders in 2005–2009. Przegl Epidemiol. 2010;64:313–7.

    PubMed  Google Scholar 

  9. 9.

    • Ghannoum MA, Jurevic RJ, Mukherjee PK, et al. Characterization of the oral fungal microbiome (mycobiome) in healthy individuals. PLoS Pathog. 2010;6:e1000713. One of the first papers to use fungal pyrosequencing of the ribosomal ITS region to characterize commensal fungal populations in a human host.

    PubMed  Article  Google Scholar 

  10. 10.

    •• Iliev ID, Funari VA, Taylor KD, et al. Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis. Science. 2012;336:1314–7. This study elegantly demonstrated that the absence of Dectin-1 and presence of fungi predisposes mice to IBD. Bacterial and fungal pyrosequncing of wild-type and dectin-1 deficient mice was performed as well.

    PubMed  Article  CAS  Google Scholar 

  11. 11.

    Schulze J, Sonnenborn U. Yeasts in the gut: from commensals to infectious agents. Dtsch Arztebl Int. 2009;106:837–42.

    PubMed  Google Scholar 

  12. 12.

    Hamad I, Sokhna C, Raoult D, Bittar F. Molecular detection of eukaryotes in a single human stool sample from Senegal. PLoS One. 2012;7:e40888.

    PubMed  Article  CAS  Google Scholar 

  13. 13.

    Nucci M, Anaissie E. Revisiting the source of candidemia: skin or gut? Clin Infect Dis. 2001;33:1959–67.

    PubMed  Article  CAS  Google Scholar 

  14. 14.

    Odds FC. Candida infections: an overview. Crit Rev Microbiol. 1987;15:1–5.

    PubMed  Article  CAS  Google Scholar 

  15. 15.

    Pizzo PA, Poplack DG, editors. Principles and practice of pediatric oncology. 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2011.

    Google Scholar 

  16. 16.

    Miranda LN, van der Heijden IM, Costa SF, et al. Candida colonisation as a source for candidaemia. J Hosp Infect. 2009;72:9–16.

    PubMed  Article  CAS  Google Scholar 

  17. 17.

    Berg RD. Bacterial translocation from the gastrointestinal tract. Adv Exp Med Biol. 1999;473:11–30.

    PubMed  Article  CAS  Google Scholar 

  18. 18.

    Shoham S, Levitz SM. The immune response to fungal infections. Br J Haematol. 2005;129:569–82.

    PubMed  Article  Google Scholar 

  19. 19.

    Rosen GP, Nielsen K, Glenn S, et al. Invasive fungal infections in pediatric oncology patients: 11-year experience at a single institution. J Pediatr Hematol Oncol. 2005;27:135–40.

    PubMed  Article  Google Scholar 

  20. 20.

    Pasqualotto AC, Nedel WL, Machado TS, Severo LC. Risk factors and outcome for nosocomial breakthrough candidaemia. J Infect. 2006;52:216–22.

    PubMed  Article  CAS  Google Scholar 

  21. 21.

    Standaert-Vitse A, Sendid B, Joossens M, et al. Candida albicans colonization and ASCA in familial Crohn's disease. Am J Gastroenterol. 2009;104:1745–53.

    PubMed  Article  CAS  Google Scholar 

  22. 22.

    Ksiadzyna D, Semianow-Wejchert J, Nawrot U, et al. Serum concentration of interleukin 10, anti-mannan Candida antibodies and the fungal colonization of the gastrointestinal tract in patients with ulcerative colitis. Adv Med Sci. 2009;54:170–6.

    PubMed  Article  CAS  Google Scholar 

  23. 23.

    Zwolinska-Wcislo M, Brzozowski T, Budak A, et al. Effect of Candida colonization on human ulcerative colitis and the healing of inflammatory changes of the colon in the experimental model of colitis ulcerosa. J Physiol Pharmacol. 2009;60:107–18.

    PubMed  CAS  Google Scholar 

  24. 24.

    Zwolinska-Wcislo M, Brzozowski T, Mach T, et al. Are probiotics effective in the treatment of fungal colonization of the gastrointestinal tract? experimental and clinical studies. J Physiol Pharmacol. 2006;57 Suppl 9:35–49.

    PubMed  Google Scholar 

  25. 25.

    Hube B. From commensal to pathogen: stage- and tissue-specific gene expression of Candida albicans. Curr Opin Microbiol. 2004;7:336–41.

    PubMed  Article  CAS  Google Scholar 

  26. 26.

    Savage DC, Dubos RJ. Localization of indigenous yeast in the murine stomach. J Bacteriol. 1967;94:1811–6.

    PubMed  CAS  Google Scholar 

  27. 27.

    Koh AY, Kohler JR, Coggshall KT, et al. Mucosal damage and neutropenia are required for Candida albicans dissemination. PLoS Pathog. 2008;4:e35.

    PubMed  Article  Google Scholar 

  28. 28.

    Pope LM, Cole GT, Guentzel MN, Berry LJ. Systemic and gastrointestinal candidiasis of infant mice after intragastric challenge. Infect Immun. 1979;25:702–7.

    PubMed  CAS  Google Scholar 

  29. 29.

    Field LH, Pope LM, Cole GT, et al. Persistence and spread of Candida albicans after intragastric inoculation of infant mice. Infect Immun. 1981;31:783–91.

    PubMed  CAS  Google Scholar 

  30. 30.

    Kennedy MJ, Volz PA. Effect of various antibiotics on gastrointestinal colonization and dissemination by Candida albicans. Sabouraudia. 1985;23:265–73.

    PubMed  Article  CAS  Google Scholar 

  31. 31.

    Samonis G, Anaissie EJ, Rosenbaum B, Bodey GP. A model of sustained gastrointestinal colonization by Candida albicans in healthy adult mice. Infect Immun. 1990;58:1514–7.

    PubMed  CAS  Google Scholar 

  32. 32.

    Wiesner SM, Jechorek RP, Garni RM, et al. Gastrointestinal colonization by Candida albicans mutant strains in antibiotic-treated mice. Clin Diagn Lab Immunol. 2001;8:192–5.

    PubMed  CAS  Google Scholar 

  33. 33.

    White SJ, Rosenbach A, Lephart P, et al. Self-regulation of Candida albicans population size during GI colonization. PLoS Pathog. 2007;3:e184.

    PubMed  Article  Google Scholar 

  34. 34.

    Schofield DA, Westwater C, Balish E. Divergent chemokine, cytokine and beta-defensin responses to gastric candidiasis in immunocompetent C57BL/6 and BALB/c mice. J Med Microbiol. 2005;54:87–92.

    PubMed  Article  CAS  Google Scholar 

  35. 35.

    Wells CL, Maddaus MA, Reynolds CM, et al. Role of anaerobic flora in the translocation of aerobic and facultatively anaerobic intestinal bacteria. Infect Immun. 1987;55:2689–94.

    PubMed  CAS  Google Scholar 

  36. 36.

    Savage DC. Microbial interference between indigenous yeast and lactobacilli in the rodent stomach. J Bacteriol. 1969;98:1278–83.

    PubMed  CAS  Google Scholar 

  37. 37.

    Noverr MC, Huffnagle GB. Regulation of Candida albicans morphogenesis by fatty acid metabolites. Infect Immun. 2004;72:6206–10.

    PubMed  Article  CAS  Google Scholar 

  38. 38.

    Noverr MC, Noggle RM, Toews GB, Huffnagle GB. Role of antibiotics and fungal microbiota in driving pulmonary allergic responses. Infect Immun. 2004;72:4996–5003.

    PubMed  Article  CAS  Google Scholar 

  39. 39.

    Wagner RD, Pierson C, Warner T, et al. Probiotic effects of feeding heat-killed Lactobacillus acidophilus and Lactobacillus casei to Candida albicans-colonized immunodeficient mice. J Food Prot. 2000;63:638–44.

    PubMed  CAS  Google Scholar 

  40. 40.

    Manzoni P, Mostert M, Leonessa ML, et al. Oral supplementation with Lactobacillus casei subspecies rhamnosus prevents enteric colonization by Candida species in preterm neonates: a randomized study. Clin Infect Dis. 2006;42:1735–42.

    PubMed  Article  CAS  Google Scholar 

  41. 41.

    Hatakka K, Ahola AJ, Yli-Knuuttila H, et al. Probiotics reduce the prevalence of oral candida in the elderly–a randomized controlled trial. J Dent Res. 2007;86:125–30.

    PubMed  Article  CAS  Google Scholar 

  42. 42.

    Mason KL, Erb Downward JR, Falkowski NR, et al. Interplay between the gastric bacterial microbiota and Candida albicans during postantibiotic recolonization and gastritis. Infect Immun. 2012;80:150–8.

    PubMed  Article  CAS  Google Scholar 

  43. 43.

    Mason KL, Erb Downward JR, Mason KD, et al. Candida albicans and bacterial microbiota interactions in the cecum during recolonization following broad-spectrum antibiotic therapy. Infect Immun. 2012;80:3371–80.

    PubMed  Article  CAS  Google Scholar 

  44. 44.

    Taur Y, Xavier JB, Lipuma L, et al. Intestinal domination and the risk of bacteremia in patients undergoing allogeneic hematopoietic stem cell transplantation. Clin Infect Dis. 2012;55:905–14.

    PubMed  Article  CAS  Google Scholar 

  45. 45.

    Farah CS, Elahi S, Pang G, et al. T cells augment monocyte and neutrophil function in host resistance against oropharyngeal candidiasis. Infect Immun. 2001;69:6110–8.

    PubMed  Article  CAS  Google Scholar 

  46. 46.

    Jones-Carson J, Vazquez-Torres A, Warner T, Balish E. Disparate requirement for T cells in resistance to mucosal and acute systemic candidiasis. Infect Immun. 2000;68:2363–5.

    PubMed  Article  CAS  Google Scholar 

  47. 47.

    Cleveland WW, Fogel BJ, Brown WT, Kay HE. Foetal thymic transplant in a case of Digeorge's syndrome. Lancet. 1968;2:1211–4.

    PubMed  Article  CAS  Google Scholar 

  48. 48.

    McCarthy GM, Mackie ID, Koval J, et al. Factors associated with increased frequency of HIV-related oral candidiasis. J Oral Pathol Med. 1991;20:332–6.

    PubMed  Article  CAS  Google Scholar 

  49. 49.

    Scully C, el-Kabir M, Samaranayake LP. Candida and oral candidosis: a review. Crit Rev Oral Biol Med. 1994;5:125–57.

    PubMed  CAS  Google Scholar 

  50. 50.

    Helstrom PB, Balish E. Effect of oral tetracycline, the microbial flora, and the athymic state on gastrointestinal colonization and infection of BALB/c mice with Candida albicans. Infect Immun. 1979;23:764–74.

    PubMed  CAS  Google Scholar 

  51. 51.

    Jensen J, Warner T, Balish E. Resistance of SCID mice to Candida albicans administered intravenously or colonizing the gut: role of polymorphonuclear leukocytes and macrophages. J Infect Dis. 1993;167:912–9.

    PubMed  Article  CAS  Google Scholar 

  52. 52.

    Boyne R, Arthur JR. The response of selenium-deficient mice to Candida albicans infection. J Nutr. 1986;116:816–22.

    PubMed  CAS  Google Scholar 

  53. 53.

    Mullick A, Elias M, Harakidas P, et al. Gene expression in HL60 granulocytoids and human polymorphonuclear leukocytes exposed to Candida albicans. Infect Immun. 2004;72:414–29.

    PubMed  Article  CAS  Google Scholar 

  54. 54.

    Cantorna MT, Balish E. Mucosal and systemic candidiasis in congenitally immunodeficient mice. Infect Immun. 1990;58:1093–100.

    PubMed  CAS  Google Scholar 

  55. 55.

    Brown GD. Innate antifungal immunity: the key role of phagocytes. Annu Rev Immunol. 2011;29:1–21.

    PubMed  Article  CAS  Google Scholar 

  56. 56.

    Saijo S, Fujikado N, Furuta T, et al. Dectin-1 is required for host defense against Pneumocystis carinii but not against Candida albicans. Nat Immunol. 2007;8:39–46.

    PubMed  Article  CAS  Google Scholar 

  57. 57.

    Taylor PR, Tsoni SV, Willment JA, et al. Dectin-1 is required for beta-glucan recognition and control of fungal infection. Nat Immunol. 2007;8:31–8.

    PubMed  Article  CAS  Google Scholar 

  58. 58.

    Werner JL, Metz AE, Horn D, et al. Requisite role for the dectin-1 beta-glucan receptor in pulmonary defense against Aspergillus fumigatus. J Immunol. 2009;182:4938–46.

    PubMed  Article  CAS  Google Scholar 

  59. 59.

    • Carvalho A, Giovannini G, De Luca A, et al. Dectin-1 isoforms contribute to distinct Th1/Th17 cell activation in mucosal candidiasis. Cell Mol Immunol. 2012;9:276–86. One of three papers (see ref 62 and 63) investigating the role of Dectin-1 and GI colonization. Here Dectin-1 appeared to have a role in susceptibility or resistance, depending on the mouse strain.

    PubMed  Article  CAS  Google Scholar 

  60. 60.

    Hise AG, Tomalka J, Ganesan S, et al. An essential role for the NLRP3 inflammasome in host defense against the human fungal pathogen Candida albicans. Cell Host Microbe. 2009;5:487–97.

    PubMed  Article  CAS  Google Scholar 

  61. 61.

    Ferwerda B, Ferwerda G, Plantinga TS, et al. Human dectin-1 deficiency and mucocutaneous fungal infections. N Engl J Med. 2009;361:1760–7.

    PubMed  Article  CAS  Google Scholar 

  62. 62.

    • Gales A, Conduche A, Bernad J, et al. PPARgamma controls dectin-1 expression required for host antifungal defense against Candida albicans. PLoS Pathog. 2010;6:e1000714. One of three papers (see ref 59 and 63) investigating the role of Dectin-1 and GI colonization. Here absence of dectin-1 in murine macrophages leads to higher Candida GI colonization.

    PubMed  Article  Google Scholar 

  63. 63.

    • Vautier S, Drummond RA, Redelinghuys P, et al. Dectin-1 is not required for controlling Candida albicans colonization of the gastrointestinal tract. Infect Immun. 2012;80:4216–22. One of three papers (see ref 59 and 62) investigating the role of Dectin-1 and GI colonization. Here dectin-1 appearred to have no role in GI colonization, but only when mice were cohoused, further emphasizing the importance of the gut microbiota.

    PubMed  Article  CAS  Google Scholar 

  64. 64.

    Denning TL, Norris BA, Medina-Contreras O, et al. Functional specializations of intestinal dendritic cell and macrophage subsets that control Th17 and regulatory T cell responses are dependent on the T cell/APC ratio, source of mouse strain, and regional localization. J Immunol. 2011;187:733–47.

    PubMed  Article  CAS  Google Scholar 

  65. 65.

    Friswell MK, Gika H, Stratford IJ, et al. Site and strain-specific variation in gut microbiota profiles and metabolism in experimental mice. PLoS One. 2010;5:e8584.

    PubMed  Article  Google Scholar 

  66. 66.

    Ivanov II, Atarashi K, Manel N, et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell. 2009;139:485–98.

    PubMed  Article  CAS  Google Scholar 

  67. 67.

    Plantinga TS, van der Velden WJ, Ferwerda B, et al. Early stop polymorphism in human DECTIN-1 is associated with increased candida colonization in hematopoietic stem cell transplant recipients. Clin Infect Dis. 2009;49:724–32.

    PubMed  Article  CAS  Google Scholar 

  68. 68.

    Rosentul DC, Plantinga TS, Oosting M, et al. Genetic variation in the dectin-1/CARD9 recognition pathway and susceptibility to candidemia. J Infect Dis. 2011;204:1138–45.

    PubMed  Article  CAS  Google Scholar 

  69. 69.

    Park H, Li Z, Yang XO, et al. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol. 2005;6:1133–41.

    PubMed  Article  CAS  Google Scholar 

  70. 70.

    Harrington LE, Hatton RD, Mangan PR, et al. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol. 2005;6:1123–32.

    PubMed  Article  CAS  Google Scholar 

  71. 71.

    Gaffen SL, Hernandez-Santos N, Peterson AC. IL-17 signaling in host defense against Candida albicans. Immunol Res. 2011;50:181–7.

    PubMed  Article  CAS  Google Scholar 

  72. 72.

    Huang W, Na L, Fidel PL, Schwarzenberger P. Requirement of interleukin-17A for systemic anti-Candida albicans host defense in mice. J Infect Dis. 2004;190:624–31.

    PubMed  Article  CAS  Google Scholar 

  73. 73.

    De Luca A, Zelante T, D'Angelo C, et al. IL-22 defines a novel immune pathway of antifungal resistance. Mucosal Immunol. 2010;3:361–73.

    PubMed  Article  Google Scholar 

  74. 74.

    Conti HR, Shen F, Nayyar N, et al. Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis. J Exp Med. 2009;206:299–311.

    PubMed  Article  CAS  Google Scholar 

  75. 75.

    Zelante T, De Luca A, Bonifazi P, et al. IL-23 and the Th17 pathway promote inflammation and impair antifungal immune resistance. Eur J Immunol. 2007;37:2695–706.

    PubMed  Article  CAS  Google Scholar 

  76. 76.

    Zheng Y, Valdez PA, Danilenko DM, et al. Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat Med. 2008;14:282–9.

    PubMed  Article  CAS  Google Scholar 

  77. 77.

    Del Sero G, Mencacci A, Cenci E, et al. Antifungal type 1 responses are upregulated in IL-10-deficient mice. Microbes Infect. 1999;1:1169–80.

    PubMed  Article  Google Scholar 

  78. 78.

    Jawhara S, Thuru X, Standaert-Vitse A, et al. Colonization of mice by Candida albicans is promoted by chemically induced colitis and augments inflammatory responses through galectin-3. J Infect Dis. 2008;197:972–80.

    PubMed  Article  CAS  Google Scholar 

  79. 79.

    Rosenbach A, Dignard D, Pierce JV, et al. Adaptations of Candida albicans for growth in the mammalian intestinal tract. Eukaryot Cell. 2010;9:1075–86.

    PubMed  Article  CAS  Google Scholar 

  80. 80.

    • Pierce JV, Kumamoto CA. Variation in Candida albicans EFG1 expression enables host-dependent changes in colonizing fungal populations. MBio. 2012;3:e00117–00112. This paper is one of the first to show that regulation of fungal genes can modulate colonization in the mammalian GI tract.

    PubMed  Article  CAS  Google Scholar 

  81. 81.

    Rahman D, Mistry M, Thavaraj S, et al. Murine model of concurrent oral and vaginal Candida albicans colonization to study epithelial host-pathogen interactions. Microbes Infect. 2007;9:615–22.

    PubMed  Article  CAS  Google Scholar 

  82. 82.

    Taylor BN, Fichtenbaum C, Saavedra M, et al. In vivo virulence of Candida albicans isolates causing mucosal infections in people infected with the human immunodeficiency virus. J Infect Dis. 2000;182:955–9.

    PubMed  Article  CAS  Google Scholar 

  83. 83.

    Rehli M. Of mice and men: species variations of Toll-like receptor expression. Trends Immunol. 2002;23:375–8.

    PubMed  Article  CAS  Google Scholar 

  84. 84.

    Jiang X, Shen C, Yu H, et al. Differences in innate immune responses correlate with differences in murine susceptibility to Chlamydia muridarum pulmonary infection. Immunology. 2010;129:556–66.

    PubMed  Article  CAS  Google Scholar 

  85. 85.

    Gibbons DL, Spencer J. Mouse and human intestinal immunity: same ballpark, different players; different rules, same score. Mucosal Immunol. 2011;4:148–57.

    PubMed  Article  CAS  Google Scholar 

Download references

Conflict of Interest

A. Koh has received grants from Global Probiotics Council, Children's Cancer Fund, Children's Clinical Research Advisory Committee (Children's Medical Center Dallas) and has sponsored research collaboration with Regeneron Pharmaceuticals, Inc.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Andrew Y. Koh.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Koh, A.Y. Gastrointestinal Colonization of Fungi. Curr Fungal Infect Rep 7, 144–151 (2013). https://doi.org/10.1007/s12281-013-0133-2

Download citation

Keywords

  • Gastrointestinal
  • Colonization
  • Pathobiont
  • Commensal
  • Microbiota
  • Candida
  • Inflammatory bowel disease
  • Th17
  • Dectin