Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

The gut mycobiota: insights into analysis, environmental interactions and role in gastrointestinal diseases

Abstract

The gut microbiota is a dense and diverse ecosystem that is involved in many physiological functions as well as in disease pathogenesis. It is dominated by bacteria, which have been extensively studied in the past 15 years; however, other microorganisms, such as fungi, phages, archaea and protists, are also present in the gut microbiota. Exploration of the fungal component, namely, the mycobiota, is at an early stage, and several specific technical challenges are associated with mycobiota analysis. The number of fungi in the lower gastrointestinal tract is far lower than that of bacteria, but fungal cells are much larger and much more complex than bacterial cells. In addition, a role of the mycobiota in disease, notably in IBD, is indicated by both descriptive data in humans and mechanistic data in mice. Interactions between bacteria and fungi within the gut, their functional roles and their interplay with the host and its immune system are fascinating areas that researchers are just beginning to investigate. In this Review, we discuss the newest data on the gut mycobiota and explore both the technical aspects of its study and its role in health and gastrointestinal diseases.

Key points

  • Interest in the study of the fungal microbiota has been rising over the past decade, resulting in the accumulation of various data sets that describe the mycobiota in health and disease.

  • This young research area requires standardization of techniques and bioinformatic analysis, as well as complete, curated databases, to reach a level of insight similar to that of the bacterial microbiota.

  • Similar to the bacterial microbiota, environmental conditions, in particular diet, considerably influence the fungal microbiota.

  • Deciphering the multitude of interactions between bacteria and fungi in the gut and in other niches is one of the most promising areas of investigation for gut microbiota manipulation.

  • Many findings now demonstrate that the gut mycobiota can strongly influence the host immune system, but considerable research is still needed to better characterize these interactions.

  • Current observations of the direct or indirect effects of the fungal microbiota on gastrointestinal diseases advocate further investigation of the mycobiota composition and means of controlling its diversity.

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

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Complete process for mycobiota analysis.
Fig. 2: Healthy mycobiota and its evolution with environmental factors.
Fig. 3: Fungi–bacterial interactions.
Fig. 4: Overview of the immune response to fungi.

Similar content being viewed by others

References

  1. Sender, R., Fuchs, S. & Milo, R. Revised estimates for the number of human and bacteria cells in the body. PLOS Biol. 14, e1002533 (2016).

    PubMed  PubMed Central  Google Scholar 

  2. Richard, M. L., Lamas, B., Liguori, G., Hoffmann, T. W. & Sokol, H. Gut fungal microbiota: the Yin and Yang of inflammatory bowel disease. Inflamm. Bowel Dis. 21, 656–665 (2015).

    PubMed  Google Scholar 

  3. Scupham, A. J. et al. Abundant and diverse fungal microbiota in the murine intestine. Appl. Environ. Microbiol. 72, 793–801 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Ott, S. J. et al. Fungi and inflammatory bowel diseases: alterations of composition and diversity. Scand. J. Gastroenterol. 43, 831–841 (2008).

    CAS  PubMed  Google Scholar 

  5. Scanlan, P. D. & Marchesi, J. R. Micro-eukaryotic diversity of the human distal gut microbiota: qualitative assessment using culture-dependent and -independent analysis of faeces. ISME J. 2, 1183–1193 (2008).

    CAS  PubMed  Google Scholar 

  6. Ghannoum, M. A. et al. Characterization of the oral fungal microbiome (mycobiome) in healthy individuals. PLOS Pathog. 6, e1000713 (2010).

    PubMed  PubMed Central  Google Scholar 

  7. Mukherjee, P. K. et al. Oral mycobiome analysis of HIV-infected patients: identification of Pichia as an antagonist of opportunistic fungi. PLOS Pathog. 10, e1003996 (2014).

    PubMed  PubMed Central  Google Scholar 

  8. Ackerman, A. L. & Underhill, D. M. The mycobiome of the human urinary tract: potential roles for fungi in urology. Ann. Transl Med. 5, 31 (2017).

    PubMed  PubMed Central  Google Scholar 

  9. Bradford, L. L. & Ravel, J. The vaginal mycobiome: a contemporary perspective on fungi in women’s health and diseases. Virulence 8, 342–351 (2017).

    PubMed  Google Scholar 

  10. Tipton, L., Ghedin, E. & Morris, A. The lung mycobiome in the next-generation sequencing era. Virulence 8, 334–341 (2017).

    CAS  PubMed  Google Scholar 

  11. Ward, T. L., Knights, D. & Gale, C. A. Infant fungal communities: current knowledge and research opportunities. BMC Med. 15, 30 (2017).

    PubMed  PubMed Central  Google Scholar 

  12. Wheeler, M. L., Limon, J. J. & Underhill, D. M. Immunity to commensal fungi: detente and disease. Annu. Rev. Pathol. 12, 359–385 (2017).

    CAS  PubMed  Google Scholar 

  13. Huseyin, C. E., O’Toole, P. W., Cotter, P. D. & Scanlan, P. D. Forgotten fungi-the gut mycobiome in human health and disease. FEMS Microbiol. Rev. 41, 479–511 (2017).

    CAS  PubMed  Google Scholar 

  14. Mukherjee, P. K. et al. Mycobiota in gastrointestinal diseases. Nat. Rev. Gastroenterol. Hepatol. 12, 77–87 (2015).

    PubMed  Google Scholar 

  15. Borges, F. M. et al. Fungal diversity of human gut microbiota among eutrophic, overweight, and obese individuals based on aerobic culture-dependent approach. Curr. Microbiol. 75, 726–735 (2018).

    CAS  PubMed  Google Scholar 

  16. Hamad, I. et al. Culturomics and amplicon-based metagenomic approaches for the study of fungal population in human gut microbiota. Sci. Rep. 7, 16788 (2017).

    PubMed  PubMed Central  Google Scholar 

  17. Gouba, N., Raoult, D. & Drancourt, M. Plant and fungal diversity in gut microbiota as revealed by molecular and culture investigations. PLOS ONE 8, e59474 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Becker, P. T. et al. Identification of filamentous fungi isolates by MALDI-TOF mass spectrometry: clinical evaluation of an extended reference spectra library. Med. Mycol. 52, 826–834 (2014).

    CAS  PubMed  Google Scholar 

  19. Sanguinetti, M. & Posteraro, B. Identification of molds by matrix-assisted laser desorption ionization-time of flight mass spectrometry. J. Clin. Microbiol. 55, 369–379 (2017).

    PubMed  PubMed Central  Google Scholar 

  20. Qin, J. et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464, 59–65 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Donovan, P. D., Gonzalez, G., Higgins, D. G., Butler, G. & Ito, K. Identification of fungi in shotgun metagenomics datasets. PLOS ONE 13, e0192898 (2018).

    PubMed  PubMed Central  Google Scholar 

  22. Lewis, J. D. et al. Inflammation, antibiotics, and diet as environmental stressors of the gut microbiome in pediatric Crohn’s disease. Cell Host Microbe 18, 489–500 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Vesty, A., Biswas, K., Taylor, M. W., Gear, K. & Douglas, R. G. Evaluating the impact of DNA extraction method on the representation of human oral bacterial and fungal communities. PLOS ONE 12, e0169877 (2017).

    PubMed  PubMed Central  Google Scholar 

  24. Huseyin, C. E., Rubio, R. C., O’Sullivan, O., Cotter, P. D. & Scanlan, P. D. The fungal frontier: a comparative analysis of methods used in the study of the human gut mycobiome. Front. Microbiol. 8, 1432 (2017).

    PubMed  PubMed Central  Google Scholar 

  25. Costea, P. I. et al. Towards standards for human fecal sample processing in metagenomic studies. Nat. Biotechnol. 35, 1069–1076 (2017).

    CAS  PubMed  Google Scholar 

  26. Schoch, C. L. et al. Nuclear ribosomal internal transcribed spacer (ITS) region as a universal DNA barcode marker for Fungi. Proc. Natl Acad. Sci. USA 109, 6241–6246 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Bellemain, E. et al. ITS as an environmental DNA barcode for fungi: an in silico approach reveals potential PCR biases. BMC Microbiol. 10, 189 (2010).

    PubMed  PubMed Central  Google Scholar 

  28. De Filippis, F., Laiola, M., Blaiotta, G. & Ercolini, D. Different amplicon targets for sequencing-based studies of fungal diversity. Appl. Environ. Microbiol. 83, e00905–17 (2017).

    PubMed  PubMed Central  Google Scholar 

  29. Motooka, D. et al. Fungal ITS1 deep-sequencing strategies to reconstruct the composition of a 26-species community and evaluation of the gut mycobiota of healthy Japanese individuals. Front. Microbiol. 8, 238 (2017).

    PubMed  PubMed Central  Google Scholar 

  30. Usyk, M., Zolnik, C. P., Patel, H., Levi, M. H. & Burk, R. D. Novel ITS1 fungal primers for characterization of the mycobiome. mSphere 2, e00488–17 (2017).

    PubMed  PubMed Central  Google Scholar 

  31. Herrera, M. L., Vallor, A. C., Gelfond, J. A., Patterson, T. F. & Wickes, B. L. Strain-dependent variation in 18S ribosomal DNA copy numbers in Aspergillus fumigatus. J. Clin. Microbiol. 47, 1325–1332 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Kembel, S. W., Wu, M., Eisen, J. A. & Green, J. L. Incorporating 16S gene copy number information improves estimates of microbial diversity and abundance. PLOS Comput. Biol. 8, e1002743 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Stielow, J. B. et al. One fungus, which genes? Development and assessment of universal primers for potential secondary fungal DNA barcodes. Persoonia 35, 242–263 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Tang, J., Iliev, I. D., Brown, J., Underhill, D. M. & Funari, V. A. Mycobiome: approaches to analysis of intestinal fungi. J. Immunol. Methods 421, 112–121 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Kumar, S. et al. CLOTU: an online pipeline for processing and clustering of 454 amplicon reads into OTUs followed by taxonomic annotation. BMC Bioinformatics 12, 182 (2011).

    PubMed  PubMed Central  Google Scholar 

  36. White, J. R., Maddox, C., White, O., Angiuoli, S. V. & Fricke, W. F. CloVR-ITS: Automated internal transcribed spacer amplicon sequence analysis pipeline for the characterization of fungal microbiota. Microbiome 1, 6 (2013).

    PubMed  PubMed Central  Google Scholar 

  37. Caporaso, J. G. et al. QIIME allows analysis of high-throughput community sequencing data. Nat. Methods 7, 335–336 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Edgar, R. C. Search and clustering orders of magnitude faster than BLAST. Bioinformatics 26, 2460–2461 (2010).

    CAS  PubMed  Google Scholar 

  39. Schloss, P. D. et al. Introducing mothur: open-source, platform-independent, community-supported software for describing and comparing microbial communities. Appl. Environ. Microbiol. 75, 7537–7541 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Gdanetz, K., Benucci, G. M. N., Vande Pol, N. & Bonito, G. CONSTAX: a tool for improved taxonomic resolution of environmental fungal ITS sequences. BMC Bioinformatics 18, 538 (2017).

    PubMed  PubMed Central  Google Scholar 

  41. Palmer, J. M., Jusino, M. A., Banik, M. T. & Lindner, D. L. Non-biological synthetic spike-in controls and the AMPtk software pipeline improve mycobiome data. PeerJ 6, e4925 (2018).

    PubMed  PubMed Central  Google Scholar 

  42. Arbefeville, S., Harris, A. & Ferrieri, P. Comparison of sequencing the D2 region of the large subunit ribosomal RNA gene (MicroSEQ(R)) versus the internal transcribed spacer (ITS) regions using two public databases for identification of common and uncommon clinically relevant fungal species. J. Microbiol. Methods 140, 40–46 (2017).

    CAS  PubMed  Google Scholar 

  43. Nilsson, R. H. et al. Taxonomic reliability of DNA sequences in public sequence databases: a fungal perspective. PLOS ONE 1, e59 (2006).

    PubMed  PubMed Central  Google Scholar 

  44. Irinyi, L. et al. International Society of Human and Animal Mycology (ISHAM)-ITS reference DNA barcoding database—the quality controlled standard tool for routine identification of human and animal pathogenic fungi. Med. Mycol. 53, 313–337 (2015).

    CAS  PubMed  Google Scholar 

  45. Koljalg, U. et al. Towards a unified paradigm for sequence-based identification of fungi. Mol. Ecol. 22, 5271–5277 (2013).

    CAS  PubMed  Google Scholar 

  46. Ratnasingham, S. & Hebert, P. D. N. bold: the barcode of life data system (http://www.barcodinglife.org). Mol. Ecol. Notes 7, 355–364 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Schoch, C. L. et al. Finding needles in haystacks: linking scientific names, reference specimens and molecular data for fungi. Database 2014, bau061 (2014).

    PubMed  PubMed Central  Google Scholar 

  48. Nilsson, R. H. et al. Taxonomic annotation of public fungal ITS sequences from the built environment — a report from an April 10–11, 2017 workshop (Aberdeen, UK). Mycokeys 28, 65–82 (2018).

    Google Scholar 

  49. Prakash, P. Y. et al. Online databases for taxonomy and identification of pathogenic fungi and proposal for a cloud-based dynamic data network platform. J. Clin. Microbiol. 55, 1011–1024 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Sekirov, I., Russell, S. L., Antunes, L. C. & Finlay, B. B. Gut microbiota in health and disease. Physiol. Rev. 90, 859–904 (2010).

    CAS  PubMed  Google Scholar 

  51. Jiang, T. T. et al. Commensal fungi recapitulate the protective benefits of intestinal bacteria. Cell Host Microbe 22, 809–816 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Donaldson, G. P., Lee, S. M. & Mazmanian, S. K. Gut biogeography of the bacterial microbiota. Nat. Rev. Microbiol. 14, 20–32 (2016).

    CAS  PubMed  Google Scholar 

  53. Hallen-Adams, H. E., Kachman, S. D., Kim, J., Legge, R. M. & Martinez, I. Fungi inhabiting the healthy human gastrointestinal tract: a diverse and dynamic community. Fungal Ecol. 15, 9–17 (2015).

    Google Scholar 

  54. Nash, A. K. et al. The gut mycobiome of the Human Microbiome Project healthy cohort. Microbiome 5, 153 (2017).

    PubMed  PubMed Central  Google Scholar 

  55. Hallen-Adams, H. E. & Suhr, M. J. Fungi in the healthy human gastrointestinal tract. Virulence 8, 352–358 (2017).

    CAS  PubMed  Google Scholar 

  56. Suhr, M. J. & Hallen-Adams, H. E. The human gut mycobiome: pitfalls and potentials—a mycologist’s perspective. Mycologia 107, 1057–1073 (2015).

    CAS  PubMed  Google Scholar 

  57. Auchtung, T. A. et al. Investigating colonization of the healthy adult gastrointestinal tract by fungi. mSphere 3, e00092–18 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Strati, F. et al. Age and gender affect the composition of fungal population of the human gastrointestinal tract. Front. Microbiol. 7, 1227 (2016).

    PubMed  PubMed Central  Google Scholar 

  59. LaTuga, M. S. et al. Beyond bacteria: a study of the enteric microbial consortium in extremely low birth weight infants. PLOS ONE 6, e27858 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Heisel, T. et al. Complementary amplicon-based genomic approaches for the study of fungal communities in humans. PLOS ONE 10, e0116705 (2015).

    PubMed  PubMed Central  Google Scholar 

  61. Schei, K. et al. Early gut mycobiota and mother-offspring transfer. Microbiome 5, 107 (2017).

    PubMed  PubMed Central  Google Scholar 

  62. Bliss, J. M., Basavegowda, K. P., Watson, W. J., Sheikh, A. U. & Ryan, R. M. Vertical and horizontal transmission of Candida albicans in very low birth weight infants using DNA fingerprinting techniques. Pediatr. Infect. Dis. J. 27, 231–235 (2008).

    PubMed  Google Scholar 

  63. Nagata, R. et al. Transmission of the major skin microbiota, Malassezia, from mother to neonate. Pediatr. Int. 54, 350–355 (2012).

    CAS  PubMed  Google Scholar 

  64. Ward, T. L. et al. Development of the human mycobiome over the first month of life and across body sites. mSystems 3, e00140–17 (2018).

    PubMed  PubMed Central  Google Scholar 

  65. Boix-Amoros, A., Martinez-Costa, C., Querol, A., Collado, M. C. & Mira, A. Multiple approaches detect the presence of fungi in human breastmilk samples from healthy mothers. Sci. Rep. 7, 13016 (2017).

    PubMed  PubMed Central  Google Scholar 

  66. David, L. A. et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 505, 559–563 (2014).

    CAS  PubMed  Google Scholar 

  67. Hoffmann, C. et al. Archaea and fungi of the human gut microbiome: correlations with diet and bacterial residents. PLOS ONE 8, e66019 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Suhr, M. J., Banjara, N. & Hallen-Adams, H. E. Sequence-based methods for detecting and evaluating the human gut mycobiome. Lett. Appl. Microbiol. 62, 209–215 (2016).

    CAS  PubMed  Google Scholar 

  69. Heisel, T. et al. High-fat diet changes fungal microbiomes and interkingdom relationships in the murine gut. mSphere 2, e00351–17 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Bamford, C. V. et al. Streptococcus gordonii modulates Candida albicans biofilm formation through intergeneric communication. Infect. Immun. 77, 3696–3704 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Hwang, G. et al. Candida albicans mannans mediate Streptococcus mutans exoenzyme GtfB binding to modulate cross-kingdom biofilm development in vivo. PLOS Pathog. 13, e1006407 (2017).

    PubMed  PubMed Central  Google Scholar 

  72. Pidwill, G. R., Rego, S., Jenkinson, H. F., Lamont, R. J. & Nobbs, A. H. Coassociation between group B streptococcus and Candida albicans promotes interactions with vaginal epithelium. Infect. Immun. 86, e00669–17 (2018).

    PubMed  PubMed Central  Google Scholar 

  73. Hoarau, G. et al. Bacteriome and mycobiome interactions underscore microbial dysbiosis in familial Crohn’s disease. MBio 7, e01250–16 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Trunk, K. et al. The type VI secretion system deploys antifungal effectors against microbial competitors. Nat. Microbiol. 3, 920–931 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Centeno, A., Davis, C. P., Cohen, M. S. & Warren, M. M. Modulation of Candida albicans attachment to human epithelial cells by bacteria and carbohydrates. Infect. Immun. 39, 1354–1360 (1983).

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Levison, M. E. & Pitsakis, P. G. Susceptibility to experimental Candida albicans urinary tract infection in the rat. J. Infect. Dis. 155, 841–846 (1987).

    CAS  PubMed  Google Scholar 

  77. Makrides, H. C. & MacFarlane, T. W. An investigation of the factors involved in increased adherence of C. albicans to epithelial cells mediated by E. coli. Microbios 38, 177–185 (1983).

    CAS  PubMed  Google Scholar 

  78. Ponomarova, O. et al. Yeast creates a niche for symbiotic lactic acid bacteria through nitrogen overflow. Cell Syst. 5, 345–357 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Li, S. et al. The opportunistic human fungal pathogen Candida albicans promotes the growth and proliferation of commensal Escherichia coli through an iron-responsive pathway. Microbiol. Res. 207, 232–239 (2018).

    CAS  PubMed  Google Scholar 

  80. Kong, E. F., Tsui, C., Kucharikova, S., Van Dijck, P. & Jabra-Rizk, M. A. Modulation of Staphylococcus aureus response to antimicrobials by the Candida albicans quorum sensing molecule farnesol. Antimicrob. Agents Chemother. 61, e01573–17 (2017).

    PubMed  PubMed Central  Google Scholar 

  81. Siavoshi, F. & Saniee, P. Vacuoles of Candida yeast as a specialized niche for Helicobacter pylori. World J. Gastroenterol. 20, 5263–5273 (2014).

    PubMed  PubMed Central  Google Scholar 

  82. van Leeuwen, P. T. et al. Interspecies Interactions between Clostridium difficile and Candida albicans. mSphere 1, e00187–16 (2016).

    PubMed  PubMed Central  Google Scholar 

  83. Lambooij, J. M., Hoogenkamp, M. A., Brandt, B. W., Janus, M. M. & Krom, B. P. Fungal mitochondrial oxygen consumption induces the growth of strict anaerobic bacteria. Fungal Genet. Biol. 109, 1–6 (2017).

    CAS  PubMed  Google Scholar 

  84. Sovran, B. et al. Enterobacteriaceae are essential for the modulation of colitis severity by fungi. Microbiome 6, 152 (2018).

    PubMed  PubMed Central  Google Scholar 

  85. Peleg, A. Y., Hogan, D. A. & Mylonakis, E. Medically important bacterial-fungal interactions. Nat. Rev. Microbiol. 8, 340–349 (2010).

    CAS  PubMed  Google Scholar 

  86. Seelig, M. S. Mechanisms by which antibiotics increase the incidence and severity of candidiasis and alter the immunological defenses. Bacteriol. Rev. 30, 442–459 (1966).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Samonis, G. et al. Prospective evaluation of effects of broad-spectrum antibiotics on gastrointestinal yeast colonization of humans. Antimicrob. Agents Chemother. 37, 51–53 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Garcia, C. et al. The human gut microbial metabolome modulates fungal growth via the TOR signaling pathway. mSphere 2, e00555–17 (2017).

    PubMed  PubMed Central  Google Scholar 

  89. Allonsius, C. N. et al. Interplay between Lactobacillus rhamnosus GG and Candida and the involvement of exopolysaccharides. Microb. Biotechnol. 10, 1753–1763 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Graham, C. E., Cruz, M. R., Garsin, D. A. & Lorenz, M. C. Enterococcus faecalis bacteriocin EntV inhibits hyphal morphogenesis, biofilm formation, and virulence of Candida albicans. Proc. Natl Acad. Sci. USA 114, 4507–4512 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Kim, Y. & Mylonakis, E. Killing of Candida albicans filaments by Salmonella enterica serovar Typhimurium is mediated by sopB effectors, parts of a type III secretion system. Eukaryot. Cell 10, 782–790 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Mayer, F. L. & Kronstad, J. W. Disarming fungal pathogens: Bacillus safensis inhibits virulence factor production and biofilm formation by Cryptococcus neoformans and Candida albicans. MBio 8, e01537–17 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Wagner, R. D. et al. Biotherapeutic effects of probiotic bacteria on candidiasis in immunodeficient mice. Infect. Immun. 65, 4165–4172 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Liang, W. et al. Lactic acid bacteria differentially regulate filamentation in two heritable cell types of the human fungal pathogen Candida albicans. Mol. Microbiol. 102, 506–519 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Cruz, M. R., Graham, C. E., Gagliano, B. C., Lorenz, M. C. & Garsin, D. A. Enterococcus faecalis inhibits hyphal morphogenesis and virulence of Candida albicans. Infect. Immun. 81, 189–200 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Cugini, C. et al. Farnesol, a common sesquiterpene, inhibits PQS production in Pseudomonas aeruginosa. Mol. Microbiol. 65, 896–906 (2007).

    CAS  PubMed  Google Scholar 

  97. Leonhardt, I. et al. The fungal quorum-sensing molecule farnesol activates innate immune cells but suppresses cellular adaptive immunity. MBio 6, e00143 (2015).

    PubMed  PubMed Central  Google Scholar 

  98. Jabra-Rizk, M. A., Meiller, T. F., James, C. E. & Shirtliff, M. E. Effect of farnesol on Staphylococcus aureus biofilm formation and antimicrobial susceptibility. Antimicrob. Agents Chemother. 50, 1463–1469 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Jang, J. E. et al. The effect of rice with Aspergillus terreus on lipid metabolism in rats. Korean J. Food Sci. Technol. 47, 658–666 (2015).

    Google Scholar 

  100. Sokol, H. et al. Fungal microbiota dysbiosis in IBD. Gut 66, 1039–1048 (2017).

    CAS  PubMed  Google Scholar 

  101. Everard, A., Matamoros, S., Geurts, L., Delzenne, N. M. & Cani, P. D. Saccharomyces boulardii administration changes gut microbiota and reduces hepatic steatosis, low-grade inflammation, and fat mass in obese and type 2 diabetic db/db mice. MBio 5, e01011–14 (2014).

    PubMed  PubMed Central  Google Scholar 

  102. Iliev, I. D. & Leonardi, I. Fungal dysbiosis: immunity and interactions at mucosal barriers. Nat. Rev. Immunol. 17, 635–646 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Netea, M. G., Joosten, L. A., van der Meer, J. W., Kullberg, B. J. & van de Veerdonk, F. L. Immune defence against Candida fungal infections. Nat. Rev. Immunol. 15, 630–642 (2015).

    CAS  PubMed  Google Scholar 

  104. Underhill, D. M. & Iliev, I. D. The mycobiota: interactions between commensal fungi and the host immune system. Nat. Rev. Immunol. 14, 405–416 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Underhill, D. M. & Pearlman, E. Immune interactions with pathogenic and commensal fungi: a two-way street. Immunity 43, 845–858 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Wheeler, M. L. et al. Immunological consequences of intestinal fungal dysbiosis. Cell Host Microbe 19, 865–873 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Bacher, P. et al. Antigen-specific expansion of human regulatory T cells as a major tolerance mechanism against mucosal fungi. Mucosal Immunol. 7, 916–928 (2014).

    CAS  PubMed  Google Scholar 

  108. Bedke, T. et al. Distinct and complementary roles for Aspergillus fumigatus-specific Tr1 and Foxp3 + regulatory T cells in humans and mice. Immunol. Cell Biol. 92, 659–670 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Bourgeois, C. & Kuchler, K. Fungal pathogens-a sweet and sour treat for toll-like receptors. Front. Cell. Infect. Microbiol. 2, 142 (2012).

    PubMed  PubMed Central  Google Scholar 

  110. Plato, A., Hardison, S. E. & Brown, G. D. Pattern recognition receptors in antifungal immunity. Semin. Immunopathol. 37, 97–106 (2015).

    CAS  PubMed  Google Scholar 

  111. Eliaz, I. The role of galectin-3 as a marker of cancer and inflammation in a stage IV ovarian cancer patient with underlying pro-inflammatory comorbidities. Case Rep. Oncol. 6, 343–349 (2013).

    PubMed  PubMed Central  Google Scholar 

  112. Srivatsan, V., George, M. & Shanmugam, E. Utility of galectin-3 as a prognostic biomarker in heart failure: where do we stand? Eur. J. Prev. Cardiol. 22, 1096–1110 (2015).

    Google Scholar 

  113. Linden, J. R., Kunkel, D., Laforce-Nesbitt, S. S. & Bliss, J. M. The role of galectin-3 in phagocytosis of Candida albicans and Candida parapsilosis by human neutrophils. Cell. Microbiol. 15, 1127–1142 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  114. Vautier, S., MacCallum, D. M. & Brown, G. D. C-Type lectin receptors and cytokines in fungal immunity. Cytokine 58, 89–99 (2012).

    CAS  PubMed  Google Scholar 

  115. Li, S. S. et al. Identification of the fungal ligand triggering cytotoxic PRR-mediated NK cell killing of Cryptococcus and Candida. Nat. Commun. 9, 751 (2018).

    PubMed  PubMed Central  Google Scholar 

  116. Leonardi, I. et al. CX3CR1(+) mononuclear phagocytes control immunity to intestinal fungi. Science 359, 232–236 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Zhang, I., Pletcher, S. D., Goldberg, A. N., Barker, B. M. & Cope, E. K. Fungal microbiota in chronic airway inflammatory disease and emerging relationships with the host immune response. Front. Microbiol. 8, 2477 (2017).

    PubMed  PubMed Central  Google Scholar 

  118. Zhang, Z. et al. Peripheral lymphoid volume expansion and maintenance are controlled by gut microbiota via RALDH+dendritic cells. Immunity 44, 330–342 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  119. Fujimura, K. E. et al. Neonatal gut microbiota associates with childhood multisensitized atopy and T cell differentiation. Nat. Med. 22, 1187–1191 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  120. Fan, D. et al. Activation of HIF-1alpha and LL-37 by commensal bacteria inhibits Candida albicans colonization. Nat. Med. 21, 808–814 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  121. Zelante, T. et al. Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. Immunity 39, 372–385 (2013).

    CAS  PubMed  Google Scholar 

  122. Quinton, J. F. et al. Anti-Saccharomyces cerevisiae mannan antibodies combined with antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease: prevalence and diagnostic role. Gut 42, 788–791 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  123. Muller, S. et al. Mannan-binding lectin deficiency results in unusual antibody production and excessive experimental colitis in response to mannose-expressing mild gut pathogens. Gut 59, 1493–1500 (2010).

    CAS  PubMed  Google Scholar 

  124. Standaert-Vitse, A. et al. Candida albicans is an immunogen for anti-Saccharomyces cerevisiae antibody markers of Crohn’s disease. Gastroenterology 130, 1764–1775 (2006).

    CAS  PubMed  Google Scholar 

  125. McFarland, L. V. Systematic review and meta-analysis of Saccharomyces boulardii in adult patients. World J. Gastroenterol. 16, 2202–2222 (2010).

    PubMed  PubMed Central  Google Scholar 

  126. Jawhara, S. et al. Colonization of mice by Candida albicans is promoted by chemically induced colitis and augments inflammatory responses through galectin-3. J. Infect. Dis. 197, 972–980 (2008).

    CAS  PubMed  Google Scholar 

  127. Standaert-Vitse, A. et al. Candida albicans colonization and ASCA in familial Crohn’s disease. Am. J. Gastroenterol. 104, 1745–1753 (2009).

    CAS  PubMed  Google Scholar 

  128. Jostins, L. et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491, 119–124 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  129. Mathew, C. G. New links to the pathogenesis of Crohn disease provided by genome-wide association scans. Nat. Rev. Genet. 9, 9–14 (2008).

    CAS  PubMed  Google Scholar 

  130. Iliev, I. D. et al. Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis. Science 336, 1314–1317 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  131. Sokol, H. et al. Card9 mediates intestinal epithelial cell restitution, T-helper 17 responses, and control of bacterial infection in mice. Gastroenterology 145, 591–601 (2013).

    CAS  PubMed  Google Scholar 

  132. El Mouzan, M. et al. Fungal microbiota profile in newly diagnosed treatment-naive children with Crohn’s disease. J. Crohns Colitis 11, 586–592 (2017).

    PubMed  Google Scholar 

  133. Liguori, G. et al. Fungal dysbiosis in mucosa-associated microbiota of Crohn’s disease patients. J. Crohns Colitis 10, 296–305 (2016).

    PubMed  Google Scholar 

  134. Mukhopadhya, I. et al. The fungal microbiota of de-novo paediatric inflammatory bowel disease. Microbes Infect. 17, 304–310 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  135. Chehoud, C. et al. Fungal signature in the gut microbiota of pediatric patients with inflammatory bowel disease. Inflamm. Bowel Dis. 21, 1948–1956 (2015).

    PubMed  Google Scholar 

  136. Qiu, X. et al. Changes in the composition of intestinal fungi and their role in mice with dextran sulfate sodium-induced colitis. Sci. Rep. 5, 10416 (2015).

    PubMed  PubMed Central  Google Scholar 

  137. Tang, C. et al. Inhibition of dectin-1 signaling ameliorates colitis by inducing Lactobacillus-mediated regulatory T cell expansion in the intestine. Cell Host Microbe 18, 183–197 (2015).

    CAS  PubMed  Google Scholar 

  138. Iliev, I. D. Dectin-1 exerts dual control in the gut. Cell Host Microbe 18, 139–141 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  139. Botschuijver, S. et al. Intestinal fungal dysbiosis is associated with visceral hypersensitivity in patients with irritable bowel syndrome and rats. Gastroenterology 153, 1026–1039 (2017).

    PubMed  Google Scholar 

  140. Brennan, C. A. & Garrett, W. S. Gut microbiota, inflammation, and colorectal cancer. Annu. Rev. Microbiol. 70, 395–411 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  141. Luan, C. et al. Dysbiosis of fungal microbiota in the intestinal mucosa of patients with colorectal adenomas. Sci. Rep. 5, 7980 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  142. Richard, M. L. et al. Mucosa-associated microbiota dysbiosis in colitis associated cancer. Gut Microbes 9, 131–142 (2018).

    CAS  PubMed  Google Scholar 

  143. Gao, R. et al. Dysbiosis signature of mycobiota in colon polyp and colorectal cancer. Eur. J. Clin. Microbiol. Infect. Dis. 36, 2457–2468 (2017).

    CAS  PubMed  Google Scholar 

  144. Yang, A. M. et al. Intestinal fungi contribute to development of alcoholic liver disease. J. Clin. Invest. 127, 2829–2841 (2017).

    PubMed  PubMed Central  Google Scholar 

  145. Marchesi, J. R. & Ravel, J. The vocabulary of microbiome research: a proposal. Microbiome 3, 31 (2015).

    PubMed  PubMed Central  Google Scholar 

  146. Lachance, M. A., Gilbert, D. G. & Starmer, W. T. Yeast communities associated with Drosophila species and related flies in an eastern oak-pine forest: a comparison with western communities. J. Ind. Microbiol. 14, 484–494 (1995).

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

Both authors researched data for the article, made substantial contributions to discussion of the article content and wrote and reviewed and/or edited the manuscript before submission.

Corresponding authors

Correspondence to Mathias L. Richard or Harry Sokol.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Related links

European MetaHit project: http://www.metahit.eu/

International Nucleotide Sequence Database: http://www.insdc.org

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Richard, M.L., Sokol, H. The gut mycobiota: insights into analysis, environmental interactions and role in gastrointestinal diseases. Nat Rev Gastroenterol Hepatol 16, 331–345 (2019). https://doi.org/10.1038/s41575-019-0121-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41575-019-0121-2

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing