410
Views
5
CrossRef citations to date
0
Altmetric
Review

The important role of fungi in inflammatory bowel diseases

, &
Pages 1312-1322 | Received 25 Feb 2021, Accepted 28 Jul 2021, Published online: 15 Aug 2021

References

  • Sartor RB, Wu GD. Roles for intestinal bacteria, viruses, and fungi in pathogenesis of inflammatory bowel diseases and therapeutic approaches. Gastroenterology. 2017;152(2):327–339.e4.
  • Qiu X, Ma J, Jiao C, et al. Alterations in the mucosa-associated fungal microbiota in patients with ulcerative colitis. Oncotarget. 2017;8(64):107577–107588.
  • Sokol H, Leducq V, Aschard H, et al. Fungal microbiota dysbiosis in IBD. Gut. 2017;66(6):1039–1048.
  • Ott SJ, Kühbacher T, Musfeldt M, et al. Fungi and inflammatory bowel diseases: Alterations of composition and diversity. Scand J Gastroenterol. 2008;43(7):831–841.
  • Strati F, Di Paola M, Stefanini I, et al. Age and gender affect the composition of fungal population of the human gastrointestinal tract. Front Microbiol. 2016;7:1227.
  • Iliev ID, Leonardi I. Fungal dysbiosis: immunity and interactions at mucosal barriers. Nat Rev Immunol. 2017;17(10):635–646.
  • Lozupone CA, Stombaugh JI, Gordon JI, et al. Diversity, stability and resilience of the human gut microbiota. Nature. 2012;489(7415):220–230.
  • Suhr MJ, Banjara N, Hallen-Adams HE. Sequence-based methods for detecting and evaluating the human gut mycobiome. Lett Appl Microbiol. 2016;62(3):209–215.
  • Dollive S, Peterfreund GL, Sherrill-Mix S, et al. A tool kit for quantifying eukaryotic rRNA gene sequences from human microbiome samples. Genome Biol. 2012;13(7):R60.
  • Hoffmann C, Dollive S, Grunberg S, et al. Archaea and fungi of the human gut microbiome: correlations with diet and bacterial residents. PLOS One. 2013;8(6):e66019.
  • Miyoshi J, Sofia MA, Pierre JF. The evidence for fungus in Crohn's disease pathogenesis. Clin J Gastroenterol. 2018;11(6):449–456.
  • Liguori G, Lamas B, Richard ML, et al. Fungal dysbiosis in mucosa-associated microbiota of Crohn's disease patients. ECCOJC. 2016;10(3):296–305.
  • Qiu X, Zhang F, Yang X, et al. Changes in the composition of intestinal fungi and their role in mice with dextran sulfate sodium-induced colitis. Sci Rep. 2015;5:10416.
  • Li Q, Wang C, Tang C, et al. Dysbiosis of gut fungal microbiota is associated with mucosal inflammation in Crohn's disease. J Clin Gastroenterol. 2014;48(6):513–523.
  • Lam S, Zuo T, Ho M, et al. Review article: fungal alterations in inflammatory bowel diseases. Aliment Pharmacol Ther. 2019;50(11–12):1159–1171.
  • Limon JJ, Tang J, Li D, et al. Malassezia is associated with crohn's disease and exacerbates colitis in mouse models. Cell Host Microbe. 2019;25(3):377–388.e6.
  • Stamatiades GA, Ioannou P, Petrikkos G, et al. Fungal infections in patients with inflammatory bowel disease: a systematic review. Mycoses. 2018;61(6):366–376.
  • Schirbel A, Shouval DS, Hebecker B, et al. Intestinal epithelial cells and T cells differentially recognize and respond to Candida albicans yeast and hypha. Eur J Immunol. 2018;48(11):1826–1837.
  • Main J, McKenzie H, Yeaman GR, et al. Antibody to Saccharomyces cerevisiae (bakers' yeast) in Crohn's disease. BMJ. 1988;297(6656):1105–1106.
  • Quinton JF, Sendid B, Reumaux D, et al. Anti-Saccharomyces cerevisiae mannan antibodies combined with antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease: prevalence and diagnostic role. Gut. 1998;42(6):788–791.
  • Sutton CL, Yang H, Li Z, et al. Familial expression of anti-Saccharomyces cerevisiae mannan antibodies in affected and unaffected relatives of patients with Crohn's disease. Gut. 2000;46(1):58–63.
  • Walker LJ, Aldhous MC, Drummond HE, et al. Anti-Saccharomyces cerevisiae antibodies (ASCA) in Crohn's disease are associated with disease severity but not NOD2/CARD15 mutations. Clin Exp Immunol. 2004;135(3):490–496.
  • Hoarau G, Mukherjee PK, Gower-Rousseau C, et al. Bacteriome and mycobiome interactions underscore microbial dysbiosis in familial Crohn's disease. mBio. 2016;7(5):e01250-16.
  • Leonardi I, Li X, Semon A, et al. CX3CR1 mononuclear phagocytes control immunity to intestinal fungi. Science. 2018;359(6372):232–236.
  • Richard ML, Liguori G, Lamas B, et al. Mucosa-associated microbiota dysbiosis in colitis associated cancer. Gut Microbes. 2018;9(2):131–142.
  • Mukhopadhya I, Hansen R, Meharg C, et al. The fungal microbiota of de-novo paediatric inflammatory bowel disease. Microbes Infect. 2015;17(4):304–310.
  • Lewis JD, Chen EZ, Baldassano RN, et al. Inflammation, antibiotics, and diet as environmental stressors of the gut microbiome in pediatric Crohn's disease. Cell Host Microbe. 2015;18(4):489–500.
  • Mouzan MIE, Korolev KS, Mofarreh MAA, et al. Fungal dysbiosis predicts the diagnosis of pediatric Crohn's disease. WJG. 2018;24(39):4510–4516.
  • Hager CL, Ghannoum MA. The mycobiome: role in health and disease, and as a potential probiotic target in gastrointestinal disease. Digest Liver Dis. 2017;49(11):1171–1176.
  • Yan P-G, Li J-N. Advances in the understanding of the intestinal micro-environment and inflammatory bowel disease. Chin Med J. 2020;133(7):834–841.
  • Guan Q. A comprehensive review and update on the pathogenesis of inflammatory bowel disease. J Immunol Res. 2019;2019:7247238.
  • Drewniak A, Gazendam RP, Tool ATJ, et al. Invasive fungal infection and impaired neutrophil killing in human CARD9 deficiency. Blood. 2013;121(13):2385–2392.
  • Dalal SR, Chang EB. The microbial basis of inflammatory bowel diseases. J Clin Invest. 2014;124(10):4190–4196.
  • Goodridge HS, Reyes CN, Becker CA, et al. Activation of the innate immune receptor dectin-1 upon formation of a ‘phagocytic synapse’. Nature. 2011;472(7344):471–475.
  • Wang T, Pan D, Zhou Z, et al. Dectin-3 deficiency promotes colitis development due to impaired antifungal innate immune responses in the gut. PLOS Pathog. 2016;12(6):e1005662.
  • Moltzau Anderson J, Lipinski S, Sommer F, et al. NOD2 influences trajectories of intestinal microbiota recovery after antibiotic perturbation. Cell Mol Gastroenterol Hepatol. 2020;10(2):365–389.
  • Wagener J, Malireddi RKS, Lenardon MD, et al. Fungal chitin dampens inflammation through IL-10 induction mediated by NOD2 and TLR9 activation. PLOS Pathog. 2014;10(4):e1004050.
  • Singel KL, Segal BH. NOX2-dependent regulation of inflammation. Clin Sci. 2016;130(7):479–490.
  • Hedjoudje A, Cheurfa C, Briquez C, et al. rs2476601 polymorphism in PTPN22 is associated with Crohn's disease but not with ulcerative colitis: a meta-analysis of 16,838 cases and 13,356 controls. Ann Gastroenterol. 2017;30(2):197–208.
  • Pérez de Diego R, Sánchez-Ramón S, López-Collazo E, et al. Genetic errors of the human caspase recruitment domain-B-cell lymphoma 10-mucosa-associated lymphoid tissue lymphoma-translocation gene 1 (CBM) complex: molecular, immunologic, and clinical heterogeneity. J Allergy Clin Immunol. 2015;136(5):1139–1149.
  • Roth S, Ruland J. Caspase recruitment domain-containing protein 9 signaling in innate immunity and inflammation. Trends Immunol. 2013;34(6):243–250.
  • Malik A, Sharma D, Malireddi RKS, et al. SYK-CARD9 signaling axis promotes gut fungi-mediated inflammasome activation to restrict colitis and colon cancer. Immunity. 2018;49(3):515–530.e5.
  • Glocker E-O, Hennigs A, Nabavi M, et al. A homozygous CARD9 mutation in a family with susceptibility to fungal infections. N Engl J Med. 2009;361(18):1727–1735.
  • Sokol H, Conway KL, Zhang M, et al. Card9 mediates intestinal epithelial cell restitution, T-helper 17 responses, and control of bacterial infection in mice. Gastroenterology. 2013;145(3):591–601.e3.
  • Lamas B, Richard ML, Leducq V, et al. CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands. Nat Med. 2016;22(6):598–605.
  • 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(6086):1314–1317.
  • Zhao X-Q, Zhu L-L, Chang Q, et al. C-type lectin receptor dectin-3 mediates trehalose 6,6′-dimycolate (TDM)-induced mincle expression through CARD9/Bcl10/MALT1-dependent nuclear factor (NF)-κB activation. J Biol Chem. 2014;289(43):30052–30062.
  • Zhu L-L, Zhao X-Q, Jiang C, et al. C-type lectin receptors dectin-3 and dectin-2 form a heterodimeric pattern-recognition receptor for host defense against fungal infection. Immunity. 2013;39(2):324–334.
  • Terciolo C, Dapoigny M, Andre F. Beneficial effects of Saccharomyces boulardii CNCM I-745 on clinical disorders associated with intestinal barrier disruption. Clin Exp Gastroenterol. 2019;12:67–82.
  • Yu Y, Yang W, Li Y, et al. Enteroendocrine cells: sensing gut microbiota and regulating inflammatory bowel diseases. Inflamm Bowel Dis. 2020;26(1):11–20.
  • Chehoud C, Albenberg LG, Judge C, et al. Fungal signature in the gut microbiota of pediatric patients with inflammatory bowel disease. Inflamm Bowel Dis. 2015;21(8):1948–1956.
  • Kullberg BJ, Arendrup MC. Invasive candidiasis. N Engl J Med. 2015;373(15):1445–1456.
  • Mohammad Jafari R, Shayesteh S, Ala M, et al. Dapsone ameliorates colitis through TLR4/NF-kB pathway in TNBS induced colitis model in rat. Arch Med Res. 2021;S0188-4409(21)00076-X.
  • Li J, Chen D, Yu B, et al. Fungi in gastrointestinal tracts of human and mice: from community to functions. Microb Ecol. 2018;75(4):821–829.
  • Caër C, Wick MJ. Human intestinal mononuclear phagocytes in health and inflammatory bowel disease. Front Immunol. 2020;11:410.
  • Leonardi I, Li X, Iliev ID. Macrophage interactions with fungi and bacteria in inflammatory bowel disease. Curr Opin Gastroenterol. 2018;34(6):392–397.
  • Di Paola M, Rizzetto L, Stefanini I, et al. Comparative immunophenotyping of Saccharomyces cerevisiae and Candida spp. strains from Crohn's disease patients and their interactions with the gut microbiome. J Transl Autoimmun. 2020;3:100036.
  • Bouguen G, Chevaux J-B, Peyrin-Biroulet L. Recent advances in cytokines: therapeutic implications for inflammatory bowel diseases. World J Gastroenterol. 2011;17(5):547–556.
  • De Luca A, Carvalho A, Cunha C, et al. IL-22 and IDO1 affect immunity and tolerance to murine and human vaginal candidiasis. PLOS Pathog. 2013;9(7):e1003486.
  • Neurath MF. Cytokines in inflammatory bowel disease. Nat Rev Immunol. 2014;14(5):329–342.
  • Hedl M, Zheng S, Abraham C. The IL18RAP region disease polymorphism decreases IL-18RAP/IL-18R1/IL-1R1 expression and signaling through innate receptor-initiated pathways. J Immunol. 2014;192(12):5924–5932.
  • Pizarro TT, Cominelli F. Cytokine therapy for Crohn's disease: advances in translational research. Annu Rev Med. 2007;58:433–444.
  • Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature. 2007;448(7152):427–434.
  • McGovern D, Powrie F. The IL23 axis plays a key role in the pathogenesis of IBD. Gut. 2007;56(10):1333–1336.
  • Netea MG, Brown GD, Kullberg BJ, et al. An integrated model of the recognition of Candida albicans by the innate immune system. Nat Rev Microbiol. 2008;6(1):67–78.
  • 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(10):2695–2706.
  • Bettelli E, Korn T, Kuchroo VK. Th17: the third member of the effector T cell trilogy. Curr Opin Immunol. 2007;19(6):652–657.
  • Zhu J, Paul WE. Peripheral CD4+ T-cell differentiation regulated by networks of cytokines and transcription factors. Immunol Rev. 2010;238(1):247–262.
  • van de Veerdonk FL, Netea MG. T-cell subsets and antifungal host defenses. Curr Fungal Infect Rep. 2010;4(4):238–243.
  • Barouti N, Mainetti C, Fontao L, et al. L-tryptophan as a novel potential pharmacological treatment for wound healing via aryl hydrocarbon receptor activation. Dermatology. 2015;230(4):332–339.
  • Di Meglio P, Duarte JH, Ahlfors H, et al. Activation of the aryl hydrocarbon receptor dampens the severity of inflammatory skin conditions. Immunity. 2014;40(6):989–1001.
  • Wheeler ML, Limon JJ, Underhill DM. Immunity to commensal fungi: detente and disease. Annu Rev Pathol. 2017;12:359–385.
  • Kadow S, Jux B, Zahner SP, et al. Aryl hydrocarbon receptor is critical for homeostasis of invariant gammadelta T cells in the murine epidermis. J Immunol. 2011;187(6):3104–3110.
  • Vlachos C, Schulte BM, Magiatis P, et al. Malassezia-derived indoles activate the aryl hydrocarbon receptor and inhibit toll-like receptor-induced maturation in monocyte-derived dendritic cells. Br J Dermatol. 2012;167(3):496–505.
  • Veldhoen M, Hirota K, Westendorf AM, et al. The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins. Nature. 2008;453(7191):106–109.
  • Duarte-Silva M, Afonso PC, de Souza PR, et al. Reappraisal of antibodies against Saccharomyces cerevisiae (ASCA) as persistent biomarkers in quiescent Crohn's disease. Autoimmunity. 2019;52(1):37–47.
  • Standaert-Vitse A, Jouault T, Vandewalle P, et al. Candida albicans is an immunogen for anti-Saccharomyces cerevisiae antibody markers of Crohn's disease. Gastroenterology. 2006;130(6):1764–1775.
  • 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(7):972–980.
  • Schaffer T, Müller S, Flogerzi B, et al. Anti-Saccharomyces cerevisiae mannan antibodies (ASCA) of Crohn's patients crossreact with mannan from other yeast strains, and murine ASCA IgM can be experimentally induced with Candida albicans. Inflamm Bowel Dis. 2007;13(11):1339–1346.
  • Standaert-Vitse A, Sendid B, Joossens M, et al. Candida albicans colonization and ASCA in familial Crohn's disease. Am J Gastroenterol. 2009;104(7):1745–1753.
  • Pérez T, Balcázar JL, Ruiz-Zarzuela I, et al. Host-microbiota interactions within the fish intestinal ecosystem. Mucosal Immunol. 2010;3(4):355–360.
  • Seow CH, Stempak JM, Xu W, et al. Novel anti-glycan antibodies related to inflammatory bowel disease diagnosis and phenotype. Am J Gastroenterol. 2009;104(6):1426–1434.
  • Sovran B, Planchais J, Jegou S, et al. Enterobacteriaceae are essential for the modulation of colitis severity by fungi. Microbiome. 2018;6(1):152.
  • Castro DP, Seabra SH, Garcia ES, et al. Trypanosoma cruzi: ultrastructural studies of adhesion, lysis and biofilm formation by Serratia marcescens. Exp Parasitol. 2007;117(2):201–207.
  • Grishin A, Papillon S, Bell B, et al. The role of the intestinal microbiota in the pathogenesis of necrotizing enterocolitis. Semin Pediatr Surg. 2013;22(2):69–75.
  • Bandara HMHN, Yau JYY, Watt RM, et al. Escherichia coli and its lipopolysaccharide modulate in vitro candida biofilm formation. J Med Microbiol. 2009;58(12):1623–1631.
  • Mendes A, Mores AU, Carvalho AP, et al. Candida albicans biofilms produce more secreted aspartyl protease than the planktonic cells. Biol Pharm Bull. 2007;30(9):1813–1815.
  • Chiaro TR, Soto R, Zac Stephens W, et al. A member of the gut mycobiota modulates host purine metabolism exacerbating colitis in mice. Sci Transl Med. 2017;9(380):eaaf9044.
  • Huseyin CE, O'Toole PW, Cotter PD, et al. Forgotten fungi-the gut mycobiome in human health and disease. FEMS Microbiol Rev. 2017;41(4):479–511.
  • Albuquerque P, Casadevall A. Quorum sensing in fungi-a review. Med Mycol. 2012;50(4):337–345.
  • Schreiber D, Marx L, Felix S, et al. Anti-inflammatory effects of fungal metabolites in mouse intestine as revealed by in vitro models. Front Physiol. 2017;8:566.
  • Sivignon A, de Vallée A, Barnich N, et al. Saccharomyces cerevisiae CNCM I-3856 prevents colitis induced by AIEC bacteria in the transgenic mouse model mimicking Crohn's disease. Inflamm Bowel Dis. 2015;21(2):276–286.
  • Jiang TT, Shao T-Y, Ang WXG, et al. Commensal fungi recapitulate the protective benefits of intestinal bacteria. Cell Host Microbe. 2017;22(6):809–816.e4.
  • Rizzetto L, Ifrim DC, Moretti S, et al. Fungal chitin induces trained immunity in human monocytes during cross-talk of the host with Saccharomyces cerevisiae. J Biol Chem. 2016;291(15):7961–7972.
  • Buentke E, Heffler LC, Wilson JL, et al. Natural killer and dendritic cell contact in lesional atopic dermatitis skin-Malassezia-influenced cell interaction. J Invest Dermatol. 2002;119(4):850–857.
  • Selander C, Engblom C, Nilsson G, et al. TLR2/MyD88-dependent and -independent activation of mast cell IgE responses by the skin commensal yeast Malassezia sympodialis. J Immunol. 2009;182(7):4208–4216.
  • Suhr MJ. Characterization and investigation of fungi inhabiting the gastrointestinal tract of healthy and diseased humans. Dissertations, Theses, & Student Research in Food Science and Technology. 2015.
  • Fieber JH, Atladóttir J, Solomon DG, et al. Disseminated enteroinvasive aspergillosis in a critically ill patient without severe immunocompromise. J Surg Case Rep. 2013;2013(11):rjt091.
  • Marti Aguado D, Ballester MP, Bosca Watts MM. Invasive pulmonary aspergillosis in an immunocompromised patient with severe ulcerative colitis. Rev Esp Enfermed Digest. 2017;109(4):316–317.
  • 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(1):107–118.
  • Recinella L, Chiavaroli A, Ronci M, et al. Multidirectional pharma-toxicological study on DC. ex meisn.: an IBD-focused investigation. Antioxidants. 2020;9(2):168.
  • Ferrante C, Recinella L, Ronci M, et al. Multiple pharmacognostic characterization on hemp commercial cultivars: focus on inflorescence water extract activity. Food Chem Toxicol. 2019;125:452–461.
  • Ferrante C, Recinella L, Ronci M, et al. Protective effects induced by alcoholic Phlomis fruticosa and Phlomis herba-venti extracts in isolated rat colon: focus on antioxidant, anti-inflammatory, and antimicrobial activities in vitro. Phytother Res. 2019;33(9):2387–2400.
  • Zengin G, Ferrante C, Orlando G, et al. Chemical profiling and pharmaco-toxicological activity of Origanum sipyleum extracts: exploring for novel sources for potential therapeutic agents. J Food Biochem. 2019;43(11):e13003.
  • Zengin G, Ferrante C, Gnapi DE, et al. Comprehensive approaches on the chemical constituents and pharmacological properties of flowers and leaves of American basil (Ocimum americanum L). Food Res Int. 2019;125:108610.
  • Dalmasso G, Cottrez F, Imbert V, et al. Saccharomyces boulardii inhibits inflammatory bowel disease by trapping T cells in mesenteric lymph nodes. Gastroenterology. 2006;131(6):1812–1825.
  • Ganji-Arjenaki M, Rafieian-Kopaei M. Probiotics are a good choice in remission of inflammatory bowel diseases: a meta analysis and systematic review. J Cell Physiol. 2018;233(3):2091–2103.
  • Matijašić M, Meštrović T, Paljetak HČ, et al. Gut microbiota beyond bacteria-mycobiome, virome, archaeome, and eukaryotic parasites in IBD. Int J Mol Sci. 2020;21(8):2668.
  • Lim BO. Coriolus versicolor suppresses inflammatory bowel disease by inhibiting the expression of STAT1 and STAT6 associated with IFN-γ and IL-4 expression. Phytother Res. 2011;25(8):1257–1261.
  • Li M, Luo T, Huang Y, et al. Polysaccharide from Pycnoporus sanguineus ameliorates dextran sulfate sodium-induced colitis via helper T cells repertoire modulation and autophagy suppression. Phytother Res. 2020;34(10):2649–2664.
  • Leonardi I, Paramsothy S, Doron I, et al. Fungal trans-kingdom dynamics linked to responsiveness to fecal microbiota transplantation (FMT) therapy in ulcerative colitis. Cell Host Microbe. 2020;27(5):823–829.e3.
  • Kostovcikova K, Coufal S, Galanova N, et al. Diet rich in animal protein promotes pro-inflammatory macrophage response and exacerbates colitis in mice. Front Immunol. 2019;10:919.
  • Nagatani K, Wang S, Llado V, et al. Chitin microparticles for the control of intestinal inflammation. Inflamm Bowel Dis. 2012;18(9):1698–1710.
  • Azuma K, Osaki T, Ifuku S, et al. α-Chitin nanofibrils improve inflammatory and fibrosis responses in inflammatory bowel disease mice model. Carbohydr Polym. 2012;90(1):197–200.
  • Louis P, Mercer B, Cirone AM, et al. Dietary chitin particles called mimetic fungi ameliorate colitis in toll-like receptor 2/CD14- and sex-dependent manners. Infect Immun. 2019;87(5):e00006-19.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.