1932

Abstract

The mycobiome plays a key role in the host immune responses in homeostasis and inflammation. Recent studies suggest that an imbalance in the gut's fungi contributes to chronic, noninfectious diseases such as obesity, metabolic disorders, and cancers. Pathogenic fungi can colonize specific organs, and the gut mycobiome has been linked to the development and progression of various cancers, including colorectal, breast, head and neck, and pancreatic cancers. Some fungal species can promote tumorigenesis by triggering the complement system. However, in immunocompromised patients, fungi can also inhibit this activation and establish life-threatening infections. Interestingly, the interaction of the fungi and bacteria can also induce unique host immune responses. Recent breakthroughs and advancements in high-throughput sequencing of the gut and tumor mycobiomes are highlighting novel diagnostic and therapeutic opportunities for cancer. We discuss the latest developments in the field of cancer and the mycobiome and the potential benefits and challenges of antifungal therapies.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-pathmechdis-111523-023524
2025-01-24
2025-02-07
Loading full text...

Full text loading...

/deliver/fulltext/pathmechdis/20/1/annurev-pathmechdis-111523-023524.html?itemId=/content/journals/10.1146/annurev-pathmechdis-111523-023524&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Cui L, Morris A, Ghedin E. 2013.. The human mycobiome in health and disease. . Genome Med. 5::63
    [Crossref] [Google Scholar]
  2. 2.
    Huffnagle GB, Noverr MC. 2013.. The emerging world of the fungal microbiome. . Trends Microbiol. 21::33441
    [Crossref] [Google Scholar]
  3. 3.
    Seed PC. 2014.. The human mycobiome. . Cold Spring Harb. Perspect. Med. 5::a019810
    [Crossref] [Google Scholar]
  4. 4.
    Nash AK, Auchtung TA, Wong MC, Smith DP, Gesell JR, et al. 2017.. The gut mycobiome of the Human Microbiome Project healthy cohort. . Microbiome 5::153
    [Crossref] [Google Scholar]
  5. 5.
    Huttenhower C, Gevers D, Knight R, Abubucker S, Badger JH, et al. (Hum. Microbiome Proj. Consort.). 2012.. Structure, function and diversity of the healthy human microbiome. . Nature 486::20714
    [Crossref] [Google Scholar]
  6. 6.
    Auchtung TA, Fofanova TY, Stewart CJ, Nash AK, Wong MC, et al. 2018.. Investigating colonization of the healthy adult gastrointestinal tract by fungi. . mSphere 3::e00092-18
    [Crossref] [Google Scholar]
  7. 7.
    Raman AS, Gehrig JL, Venkatesh S, Chang HW, Hibberd MC, et al. 2019.. A sparse covarying unit that describes healthy and impaired human gut microbiota development. . Science 365:(6449):eaau4735
    [Crossref] [Google Scholar]
  8. 8.
    Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, et al. 2012.. Human gut microbiome viewed across age and geography. . Nature 486::22227
    [Crossref] [Google Scholar]
  9. 9.
    Zhang F, Aschenbrenner D, Yoo JY, Zuo T. 2022.. The gut mycobiome in health, disease, and clinical applications in association with the gut bacterial microbiome assembly. . Lancet Microbe 3::e96983
    [Crossref] [Google Scholar]
  10. 10.
    Hallen-Adams HE, Suhr MJ. 2017.. Fungi in the healthy human gastrointestinal tract. . Virulence 8::35258
    [Crossref] [Google Scholar]
  11. 11.
    Shuai M, Fu Y, Zhong HL, Gou W, Jiang Z, et al. 2022.. Mapping the human gut mycobiome in middle-aged and elderly adults: multiomics insights and implications for host metabolic health. . Gut 71::181220
    [Crossref] [Google Scholar]
  12. 12.
    Narunsky-Haziza L, Sepich-Poore GD, Livyatan I, Asraf O, Martino C, et al. 2022.. Pan-cancer analyses reveal cancer type-specific fungal ecologies and bacteriome interactions. . Cell 185::3789806
    [Crossref] [Google Scholar]
  13. 13.
    Schmidt TSB, Raes J, Bork P. 2018.. The human gut microbiome: from association to modulation. . Cell 172::1198215
    [Crossref] [Google Scholar]
  14. 14.
    Strati F, Di Paola M, Stefanini I, Albanese D, Rizzetto L, et al. 2016.. Age and gender affect the composition of fungal population of the human gastrointestinal tract. . Front. Microbiol. 7::1227
    [Crossref] [Google Scholar]
  15. 15.
    Fujimura KE, Sitarik AR, Havstad S, Lin DL, Levan S, et al. 2016.. Neonatal gut microbiota associates with childhood multisensitized atopy and T cell differentiation. . Nat. Med. 22::118791
    [Crossref] [Google Scholar]
  16. 16.
    Schei K, Avershina E, Øien T, Rudi K, Follestad T, et al. 2017.. Early gut mycobiota and mother-offspring transfer. . Microbiome 5::107. Erratum . 2021.. Microbiome 9::120
    [Google Scholar]
  17. 17.
    Cohen R, Roth FJ, Delgado E, Ahearn DG, Kalser MH. 1969.. Fungal flora of the normal human small and large intestine. . N. Engl. J. Med. 280::63841
    [Crossref] [Google Scholar]
  18. 18.
    Richard ML, Sokol H. 2019.. The gut mycobiota: insights into analysis, environmental interactions and role in gastrointestinal diseases. . Nat. Rev. Gastroenterol. Hepatol. 16::33145
    [Google Scholar]
  19. 19.
    Ghannoum MA, Jurevic RJ, Mukherjee PK, Cui F, Sikaroodi M, et al. 2010.. Characterization of the oral fungal microbiome (mycobiome) in healthy individuals. . PLOS Pathog. 6::e1000713
    [Crossref] [Google Scholar]
  20. 20.
    Coker OO, Nakatsu G, Dai RZ, Wu WKK, Wong SH, et al. 2019.. Enteric fungal microbiota dysbiosis and ecological alterations in colorectal cancer. . Gut 68::65462
    [Crossref] [Google Scholar]
  21. 21.
    Alam A, Levanduski E, Denz P, Villavicencio HS, Bhatta M, et al. 2022.. Fungal mycobiome drives IL-33 secretion and type 2 immunity in pancreatic cancer. . Cancer Cell 40::15367.e11
    [Crossref] [Google Scholar]
  22. 22.
    Aykut B, Pushalkar S, Chen R, Li Q, Abengozar R, et al. 2019.. The fungal mycobiome promotes pancreatic oncogenesis via activation of MBL. . Nature 574::26467
    [Crossref] [Google Scholar]
  23. 23.
    Di Cosola M, Cazzolla AP, Charitos IA, Ballini A, Inchingolo F, Santacroce L. 2021.. Candida albicans and oral carcinogenesis. A brief review. . J. Fungi 7::476
    [Crossref] [Google Scholar]
  24. 24.
    Chin VK, Yong VC, Chong PP, Amin Nordin S, Basir R, Abdullah M. 2020.. Mycobiome in the gut: a multiperspective review. . Mediat. Inflamm. 2020::9560684
    [Crossref] [Google Scholar]
  25. 25.
    Elaskandrany M, Patel R, Patel M, Miller G, Saxena D, Saxena A. 2021.. Fungi, host immune response, and tumorigenesis. . Am. J. Physiol. Gastrointest. Liver Physiol. 321::G21322
    [Crossref] [Google Scholar]
  26. 26.
    Li X, Saxena D. 2022.. The mycobiome-immune axis: the next frontier in pancreatic cancer. . Cancer Cell 40::12022
    [Crossref] [Google Scholar]
  27. 27.
    Dohlman AB, Klug J, Mesko M, Gao IH, Lipkin SM, et al. 2022.. A pan-cancer mycobiome analysis reveals fungal involvement in gastrointestinal and lung tumors that is predictive of survival. . Cell 185::380722
    [Crossref] [Google Scholar]
  28. 28.
    Li X, Saxena D. 2022.. The tumor mycobiome: a paradigm shift in cancer pathogenesis. . Cell 185::364851
    [Crossref] [Google Scholar]
  29. 29.
    Song Z, Schlatter D, Kennedy P, Kinkel LL, Kistler HC, et al. 2015.. Effort versus reward: preparing samples for fungal community characterization in high-throughput sequencing surveys of soils. . PLOS ONE 10::e0127234
    [Crossref] [Google Scholar]
  30. 30.
    Vallianou N, Kounatidis D, Christodoulatos GS, Panagopoulos F, Karampela I, Dalamaga M. 2021.. Mycobiome and cancer: What is the evidence?. Cancers 13::3149
    [Crossref] [Google Scholar]
  31. 31.
    Li S, Deng Y, Wang Z, Zhang Z, Kong X, et al. 2020.. Exploring the accuracy of amplicon-based internal transcribed spacer markers for a fungal community. . Mol. Ecol. Resour. 20::17084
    [Crossref] [Google Scholar]
  32. 32.
    Schoch CL, Seifert KA, Huhndorf S, Robert V, Spouge JL, et al. 2012.. Nuclear ribosomal internal transcribed spacer (ITS) region as a universal DNA barcode marker for Fungi. . PNAS 109::624146
    [Crossref] [Google Scholar]
  33. 33.
    Nilsson RH, Kristiansson E, Ryberg M, Hallenberg N, Larsson KH. 2008.. Intraspecific ITS variability in the kingdom Fungi as expressed in the international sequence databases and its implications for molecular species identification. . Evol. Bioinform. Online 4::193201
    [Crossref] [Google Scholar]
  34. 34.
    Yang RH, Su JH, Shang JJ, Wu YY, Li Y, et al. 2018.. Evaluation of the ribosomal DNA internal transcribed spacer (ITS), specifically ITS1 and ITS2, for the analysis of fungal diversity by deep sequencing. . PLOS ONE 13::e0206428
    [Crossref] [Google Scholar]
  35. 35.
    Thorsson V, Gibbs DL, Brown SD, Wolf D, Bortone DS, et al. 2018.. The immune landscape of cancer. . Immunity 48::81230.e14
    [Crossref] [Google Scholar]
  36. 36.
    Liu NN, Yi CX, Wei LQ, Zhou JA, Jiang T, et al. 2023.. The intratumor mycobiome promotes lung cancer progression via myeloid-derived suppressor cells. . Cancer Cell 41::192744.e9
    [Crossref] [Google Scholar]
  37. 37.
    Dickson I. 2019.. Fungal dysbiosis associated with colorectal cancer. . Nat. Rev. Gastroenterol. Hepatol. 16::76
    [Google Scholar]
  38. 38.
    Clay SL, Fonseca-Pereira D, Garrett WS. 2022.. Colorectal cancer: the facts in the case of the microbiota. . J. Clin. Investig. 132::e155101
    [Crossref] [Google Scholar]
  39. 39.
    Wong SH, Yu J. 2019.. Gut microbiota in colorectal cancer: mechanisms of action and clinical applications. . Nat. Rev. Gastroenterol. Hepatol. 16::690704
    [Crossref] [Google Scholar]
  40. 40.
    Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, et al. 2010.. A human gut microbial gene catalogue established by metagenomic sequencing. . Nature 464::5965
    [Crossref] [Google Scholar]
  41. 41.
    Johnson CM, Wei C, Ensor JE, Smolenski DJ, Amos CI, et al. 2013.. Meta-analyses of colorectal cancer risk factors. . Cancer Causes Control 24::120722
    [Crossref] [Google Scholar]
  42. 42.
    O'Sullivan DE, Sutherland RL, Town S, Chow K, Fan J, et al. 2022.. Risk factors for early-onset colorectal cancer: a systematic review and meta-analysis. . Clin. Gastroenterol. Hepatol. 20::122940.e5
    [Crossref] [Google Scholar]
  43. 43.
    Luan C, Xie L, Yang X, Miao H, Lv N, et al. 2015.. Dysbiosis of fungal microbiota in the intestinal mucosa of patients with colorectal adenomas. . Sci. Rep. 5::7980
    [Crossref] [Google Scholar]
  44. 44.
    Gao R, Kong C, Li H, Huang L, Qu X, et al. 2017.. Dysbiosis signature of mycobiota in colon polyp and colorectal cancer. . Eur. J. Clin. Microbiol. Infect. Dis. 36::245768
    [Crossref] [Google Scholar]
  45. 45.
    Liu NN, Jiao N, Tan JC, Wang Z, Wu D, et al. 2022.. Multi-kingdom microbiota analyses identify bacterial-fungal interactions and biomarkers of colorectal cancer across cohorts. . Nat. Microbiol. 7::23850
    [Crossref] [Google Scholar]
  46. 46.
    Qin X, Gu Y, Liu T, Wang C, Zhong W, et al. 2021.. Gut mycobiome: a promising target for colorectal cancer. . Biochim. Biophys. Acta Rev. Cancer 1875::188489
    [Crossref] [Google Scholar]
  47. 47.
    You N, Xu J, Wang L, Zhuo L, Zhou J, et al. 2021.. Fecal fungi dysbiosis in nonalcoholic fatty liver disease. . Obesity 29::35058
    [Crossref] [Google Scholar]
  48. 48.
    Lang S, Duan Y, Liu J, Torralba MG, Kuelbs C, et al. 2020.. Intestinal fungal dysbiosis and systemic immune response to fungi in patients with alcoholic hepatitis. . Hepatology 71::52238
    [Crossref] [Google Scholar]
  49. 49.
    Kociszewska D, Chan J, Thorne PR, Vlajkovic SM. 2021.. The link between gut dysbiosis caused by a high-fat diet and hearing loss. . Int. J. Mol. Sci. 22::13177
    [Crossref] [Google Scholar]
  50. 50.
    Miao ZH, Zhou WX, Cheng RY, Liang HJ, Jiang FL, et al. 2021.. Dysbiosis of intestinal microbiota in early life aggravates high-fat diet induced dysmetabolism in adult mice. . BMC Microbiol. 21::209
    [Crossref] [Google Scholar]
  51. 51.
    Song M, Chan AT, Sun J. 2020.. Influence of the gut microbiome, diet, and environment on risk of colorectal cancer. . Gastroenterology 158::32240
    [Crossref] [Google Scholar]
  52. 52.
    Conche C, Greten FR. 2018.. Fungi enter the stage of colon carcinogenesis. . Immunity 49::38486
    [Crossref] [Google Scholar]
  53. 53.
    Dmitrieva-Posocco O, Dzutsev A, Posocco DF, Hou V, Yuan W, et al. 2019.. Cell-type-specific responses to interleukin-1 control microbial invasion and tumor-elicited inflammation in colorectal cancer. . Immunity 50::16680.e7
    [Crossref] [Google Scholar]
  54. 54.
    Li X, Leonardi I, Iliev ID. 2017.. Candidalysin sets off the innate alarm. . Sci. Immunol. 2::eaao5703
    [Crossref] [Google Scholar]
  55. 55.
    Voronov E, Apte RN. 2015.. IL-1 in colon inflammation, colon carcinogenesis and invasiveness of colon cancer. . Cancer Microenviron. 8::187200
    [Crossref] [Google Scholar]
  56. 56.
    Malik A, Sharma D, Malireddi RKS, Guy CS, Chang TC, et al. 2018.. SYK-CARD9 signaling axis promotes gut fungi-mediated inflammasome activation to restrict colitis and colon cancer. . Immunity 49::51530.e5
    [Crossref] [Google Scholar]
  57. 57.
    Wang T, Fan C, Yao A, Xu X, Zheng G, et al. 2018.. The adaptor protein CARD9 protects against colon cancer by restricting mycobiota-mediated expansion of myeloid-derived suppressor cells. . Immunity 49::50414.e4
    [Crossref] [Google Scholar]
  58. 58.
    Keum N, Giovannucci E. 2019.. Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies. . Nat. Rev. Gastroenterol. Hepatol. 16::71332
    [Crossref] [Google Scholar]
  59. 59.
    Wang G, Yu Y, Wang YZ, Wang JJ, Guan R, et al. 2019.. Role of SCFAs in gut microbiome and glycolysis for colorectal cancer therapy. . J. Cell. Physiol. 234::1702349
    [Crossref] [Google Scholar]
  60. 60.
    Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, et al. 2021.. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. . CA Cancer J. Clin. 71::20949
    [Crossref] [Google Scholar]
  61. 61.
    Montelongo-Jauregui D, Lopez-Ribot JL. 2018.. Candida interactions with the oral bacterial microbiota. . J. Fungi 4::122
    [Crossref] [Google Scholar]
  62. 62.
    Diaz PI, Dongari-Bagtzoglou A. 2021.. Critically appraising the significance of the oral mycobiome. . J. Dent. Res. 100::13340
    [Crossref] [Google Scholar]
  63. 63.
    Perera M, Al-Hebshi NN, Perera I, Ipe D, Ulett GC, et al. 2017.. A dysbiotic mycobiome dominated by Candida albicans is identified within oral squamous-cell carcinomas. . J. Oral Microbiol. 9::1385369
    [Crossref] [Google Scholar]
  64. 64.
    Shelburne SA, Ajami NJ, Chibucos MC, Beird HC, Tarrand J, et al. 2015.. Implementation of a pan-genomic approach to investigate holobiont-infecting microbe interaction: a case report of a leukemic patient with invasive mucormycosis. . PLOS ONE 10::e0139851
    [Crossref] [Google Scholar]
  65. 65.
    Vesty A, Gear K, Biswas K, Radcliff FJ, Taylor MW, Douglas RG. 2018.. Microbial and inflammatory-based salivary biomarkers of head and neck squamous cell carcinoma. . Clin. Exp. Dent. Res. 4::25562
    [Crossref] [Google Scholar]
  66. 66.
    Mukherjee PK, Wang H, Retuerto M, Zhang H, Burkey B, et al. 2017.. Bacteriome and mycobiome associations in oral tongue cancer. . Oncotarget 8::9727389
    [Crossref] [Google Scholar]
  67. 67.
    Moritani K, Takeshita T, Shibata Y, Ninomiya T, Kiyohara Y, Yamashita Y. 2015.. Acetaldehyde production by major oral microbes. . Oral Dis. 21::74854
    [Crossref] [Google Scholar]
  68. 68.
    Marttila E, Bowyer P, Sanglard D, Uittamo J, Kaihovaara P, et al. 2013.. Fermentative 2-carbon metabolism produces carcinogenic levels of acetaldehyde in Candida albicans. . Mol. Oral Microbiol. 28::28191
    [Crossref] [Google Scholar]
  69. 69.
    Han YW, Wang X. 2013.. Mobile microbiome: oral bacteria in extra-oral infections and inflammation. . J. Dent. Res. 92::48591
    [Crossref] [Google Scholar]
  70. 70.
    Shay E, Sangwan N, Padmanabhan R, Lundy S, Burkey B, Eng C. 2020.. Bacteriome and mycobiome and bacteriome-mycobiome interactions in head and neck squamous cell carcinoma. . Oncotarget 11::237586
    [Crossref] [Google Scholar]
  71. 71.
    Huet MAL, Lee CZ, Rahman S. 2022.. A review on association of fungi with the development and progression of carcinogenesis in the human body. . Curr. Res. Microb. Sci. 3::100090
    [Google Scholar]
  72. 72.
    Peters BA, Wu J, Hayes RB, Ahn J. 2017.. The oral fungal mycobiome: characteristics and relation to periodontitis in a pilot study. . BMC Microbiol. 17::157
    [Crossref] [Google Scholar]
  73. 73.
    Turner SA, Butler G. 2014.. The Candida pathogenic species complex. . Cold Spring Harb. Perspect. Med. 4::a019778
    [Crossref] [Google Scholar]
  74. 74.
    Mohamed N, Litlekalsoy J, Ahmed IA, Martinsen EMH, Furriol J, et al. 2021.. Analysis of salivary mycobiome in a cohort of oral squamous cell carcinoma patients from Sudan identifies higher salivary carriage of Malassezia as an independent and favorable predictor of overall survival. . Front. Cell. Infect. Microbiol. 11::673465
    [Crossref] [Google Scholar]
  75. 75.
    Fan X, Peters BA, Jacobs EJ, Gapstur SM, Purdue MP, et al. 2018.. Drinking alcohol is associated with variation in the human oral microbiome in a large study of American adults. . Microbiome 6::59
    [Crossref] [Google Scholar]
  76. 76.
    Hartmann P, Lang S, Zeng S, Duan Y, Zhang X, et al. 2021.. Dynamic changes of the fungal microbiome in alcohol use disorder. . Front. Physiol 12::699253
    [Crossref] [Google Scholar]
  77. 77.
    Monteiro-da-Silva F, Sampaio-Maia B, Pereira Mde L, Araujo R. 2013.. Characterization of the oral fungal microbiota in smokers and non-smokers. . Eur. J. Oral Sci. 121::13235
    [Crossref] [Google Scholar]
  78. 78.
    Sajid M, Sharma P, Srivastava S, Hariprasad R, Singh H, Bharadwaj M. 2022.. Smokeless tobacco consumption induces dysbiosis of oral mycobiome: a pilot study. . Appl. Microbiol. Biotechnol. 106::564357
    [Crossref] [Google Scholar]
  79. 79.
    O'Grady I, Anderson A, O'Sullivan J. 2020.. The interplay of the oral microbiome and alcohol consumption in oral squamous cell carcinomas. . Oral Oncol. 110::105011
    [Crossref] [Google Scholar]
  80. 80.
    Theofilou VI, Alfaifi A, Montelongo-Jauregui D, Pettas E, Georgaki M, et al. 2022.. The oral mycobiome: oral epithelial dysplasia and oral squamous cell carcinoma. . J. Oral Pathol. Med. 51::41320
    [Crossref] [Google Scholar]
  81. 81.
    Krogh P, Hald B, Holmstrup P. 1987.. Possible mycological etiology of oral mucosal cancer: catalytic potential of infecting Candida albicans and other yeasts in production of N-nitrosobenzylmethylamine. . Carcinogenesis 8::154348
    [Crossref] [Google Scholar]
  82. 82.
    Bhaskaran N, Jayaraman S, Quigley C, Mamileti P, Ghannoum M, et al. 2021.. The role of Dectin-1 signaling in altering tumor immune microenvironment in the context of aging. . Front. Oncol. 11::669066
    [Crossref] [Google Scholar]
  83. 83.
    Vadovics M, Ho J, Igaz N, Alfoldi R, Rakk D, et al. 2022.. Candida albicans enhances the progression of oral squamous cell carcinoma in vitro and in vivo. . mBio 13::e0314421
    [Crossref] [Google Scholar]
  84. 84.
    Pagliari D, Saviano A, Newton EE, Serricchio ML, Dal Lago AA, et al. 2018.. Gut microbiota-immune system crosstalk and pancreatic disorders. . Mediat. Inflamm. 2018::7946431
    [Crossref] [Google Scholar]
  85. 85.
    Riquelme E, Zhang Y, Zhang L, Montiel M, Zoltan M, et al. 2019.. Tumor microbiome diversity and composition influence pancreatic cancer outcomes. . Cell 178::795806.e12
    [Crossref] [Google Scholar]
  86. 86.
    Geller LT, Barzily-Rokni M, Danino T, Jonas OH, Shental N, et al. 2017.. Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine. . Science 357::115660
    [Crossref] [Google Scholar]
  87. 87.
    Thomas RM, Jobin C. 2020.. Microbiota in pancreatic health and disease: the next frontier in microbiome research. . Nat. Rev. Gastroenterol. Hepatol. 17::5364
    [Crossref] [Google Scholar]
  88. 88.
    Zambirinis CP, Pushalkar S, Saxena D, Miller G. 2014.. Pancreatic cancer, inflammation, and microbiome. . Cancer J. 20::195202
    [Crossref] [Google Scholar]
  89. 89.
    Quintana FJ. 2013.. The aryl hydrocarbon receptor: a molecular pathway for the environmental control of the immune response. . Immunology 138::18389
    [Crossref] [Google Scholar]
  90. 90.
    Yin XF, Chen J, Mao W, Wang YH, Chen MH. 2013.. Downregulation of aryl hydrocarbon receptor expression decreases gastric cancer cell growth and invasion. . Oncol. Rep. 30::36470
    [Crossref] [Google Scholar]
  91. 91.
    Koliopanos A, Kleeff J, Xiao Y, Safe S, Zimmermann A, et al. 2002.. Increased arylhydrocarbon receptor expression offers a potential therapeutic target for pancreatic cancer. . Oncogene 21::605970
    [Crossref] [Google Scholar]
  92. 92.
    Fletcher AA, Kelly MS, Eckhoff AM, Allen PJ. 2023.. Revisiting the intrinsic mycobiome in pancreatic cancer. . Nature 620::E16
    [Crossref] [Google Scholar]
  93. 93.
    Xu F, Saxena D, Pushalkar S, Miller G. 2023.. Reply to: Revisiting the intrinsic mycobiome in pancreatic cancer. . Nature 620::E79
    [Crossref] [Google Scholar]
  94. 94.
    Okuno K, Tokunaga M, Von Hoff D, Kinugasa Y, Goel A, et al. (PDAC Biomark. Work. Group). 2023.. Intratumoral Malassezia globosa levels predict survival and therapeutic response to adjuvant chemotherapy in patients with pancreatic ductal adenocarcinoma. . Gastroenterology 165::5024.e2
    [Crossref] [Google Scholar]
  95. 95.
    Brayer KJ, Hanson JA, Cingam S, Martinez C, Ness SA, Rabinowitz I. 2023.. The inflammatory response of human pancreatic cancer samples compared to normal controls. . PLOS ONE 18::e0284232
    [Crossref] [Google Scholar]
  96. 96.
    Galloway-Pena J, Iliev ID, McAllister F. 2024.. Fungi in cancer. . Nat. Rev. Cancer 24::29598
    [Crossref] [Google Scholar]
  97. 97.
    Dohlman AB, Klug J, Mesko M, Gao IH, Lipkin SM, et al. 2022.. A pan-cancer mycobiome analysis reveals fungal involvement in gastrointestinal and lung tumors. . Cell 185::380722.e12
    [Crossref] [Google Scholar]
  98. 98.
    Das SP, Ahmed SMQ, Naik B, Laha S, Bejai V. 2021.. The human fungal pathogen Malassezia and its role in cancer. . Fungal Biol. Rev. 38::924
    [Crossref] [Google Scholar]
  99. 99.
    Zong Z, Zhou F, Zhang L. 2023.. The fungal mycobiome: a new hallmark of cancer revealed by pan-cancer analyses. . Signal Transduct. Target. Ther. 8::50
    [Crossref] [Google Scholar]
  100. 100.
    Siegel RL, Miller KD, Fuchs HE, Jemal A. 2022.. Cancer statistics, 2022. . CA Cancer J. Clin. 72::733
    [Crossref] [Google Scholar]
  101. 101.
    Dalamaga M, Polyzos SA, Karmaniolas K, Chamberland J, Lekka A, et al. 2014.. Circulating fetuin-A in patients with pancreatic cancer: a hospital-based case-control study. . Biomarkers 19::66066
    [Crossref] [Google Scholar]
  102. 102.
    Mar Rodriguez M, Perez D, Javier Chaves F, Esteve E, Marin-Garcia P, et al. 2015.. Obesity changes the human gut mycobiome. . Sci. Rep. 5::14600. Erratum . Sci. Rep. 6::21679
    [Google Scholar]
  103. 103.
    Sokol H, Leducq V, Aschard H, Pham HP, Jegou S, et al. 2017.. Fungal microbiota dysbiosis in IBD. . Gut 66::103948
    [Crossref] [Google Scholar]
  104. 104.
    Bertolini M, Ranjan A, Thompson A, Diaz PI, Sobue T, et al. 2019.. Candida albicans induces mucosal bacterial dysbiosis that promotes invasive infection. . PLOS Pathog. 15::e1007717
    [Crossref] [Google Scholar]
  105. 105.
    Mullick A, Elias M, Picard S, Bourget L, Jovcevski O, et al. 2004.. Dysregulated inflammatory response to Candida albicans in a C5-deficient mouse strain. . Infect. Immun. 72::586876
    [Crossref] [Google Scholar]
  106. 106.
    Tsoni SV, Kerrigan AM, Marakalala MJ, Srinivasan N, Duffield M, et al. 2009.. Complement C3 plays an essential role in the control of opportunistic fungal infections. . Infect. Immun. 77::367985
    [Crossref] [Google Scholar]
  107. 107.
    Rosenfeld SI, Baum J, Steigbigel RT, Leddy JP. 1976.. Hereditary deficiency of the fifth component of complement in man. II. Biological properties of C5-deficient human serum. . J. Clin. Investig. 57::163543
    [Crossref] [Google Scholar]
  108. 108.
    Socie G, Caby-Tosi MP, Marantz JL, Cole A, Bedrosian CL, et al. 2019.. Eculizumab in paroxysmal nocturnal haemoglobinuria and atypical haemolytic uraemic syndrome: 10-year pharmacovigilance analysis. . Br. J. Haematol. 185::297310
    [Crossref] [Google Scholar]
  109. 109.
    Desai JV, Kumar D, Freiwald T, Chauss D, Johnson MD, et al. 2023.. C5a-licensed phagocytes drive sterilizing immunity during systemic fungal infection. . Cell 186::280222.e22
    [Crossref] [Google Scholar]
  110. 110.
    Brouwer N, Dolman KM, van Houdt M, Sta M, Roos D, Kuijpers TW. 2008.. Mannose-binding lectin (MBL) facilitates opsonophagocytosis of yeasts but not of bacteria despite MBL binding. . J. Immunol. 180::412432
    [Crossref] [Google Scholar]
  111. 111.
    Li D, Dong B, Tong Z, Wang Q, Liu W, et al. 2012.. MBL-mediated opsonophagocytosis of Candida albicans by human neutrophils is coupled with intracellular Dectin-1-triggered ROS production. . PLOS ONE 7::e50589
    [Crossref] [Google Scholar]
  112. 112.
    Meri T, Hartmann A, Lenk D, Eck R, Wurzner R, et al. 2002.. The yeast Candida albicans binds complement regulators factor H and FHL-1. . Infect. Immun. 70::518592
    [Crossref] [Google Scholar]
  113. 113.
    Zipfel PF, Skerka C, Kupka D, Luo S. 2011.. Immune escape of the human facultative pathogenic yeast Candida albicans: the many faces of the Candida Pra1 protein. . Int. J. Med. Microbiol. 301::42330
    [Crossref] [Google Scholar]
  114. 114.
    Luo S, Dasari P, Reiher N, Hartmann A, Jacksch S, et al. 2018.. The secreted Candida albicans protein Pra1 disrupts host defense by broadly targeting and blocking complement C3 and C3 activation fragments. . Mol. Immunol. 93::26677
    [Crossref] [Google Scholar]
  115. 115.
    Speth C, Rambach G, Wurzner R, Lass-Florl C. 2008.. Complement and fungal pathogens: an update. . Mycoses 51::47796
    [Crossref] [Google Scholar]
  116. 116.
    Shiao SL, Kershaw KM, Limon JJ, You S, Yoon J, et al. 2021.. Commensal bacteria and fungi differentially regulate tumor responses to radiation therapy. . Cancer Cell 39::120213.e6
    [Crossref] [Google Scholar]
  117. 117.
    Bukavina L, Prunty M, Isali I, Calaway A, Ginwala R, et al. 2022.. Human gut mycobiome and fungal community interaction: the unknown musketeer in the chemotherapy response status in bladder cancer. . Eur. Urol. Open Sci. 43::513
    [Crossref] [Google Scholar]
  118. 118.
    Hoffmann C, Dollive S, Grunberg S, Chen J, Li H, et al. 2013.. Archaea and fungi of the human gut microbiome: correlations with diet and bacterial residents. . PLOS ONE 8::e66019
    [Crossref] [Google Scholar]
  119. 119.
    Pareek S, Kurakawa T, Das B, Motooka D, Nakaya S, et al. 2019.. Comparison of Japanese and Indian intestinal microbiota shows diet-dependent interaction between bacteria and fungi. . NPJ Biofilms Microbiomes 5::37
    [Crossref] [Google Scholar]
  120. 120.
    Hager CL, Isham N, Schrom KP, Chandra J, McCormick T, et al. 2019.. Effects of a novel probiotic combination on pathogenic bacterial-fungal polymicrobial biofilms. . mBio 10::e00338-19
    [Crossref] [Google Scholar]
  121. 121.
    Slizewska K, Markowiak-Kopec P, Slizewska W. 2020.. The role of probiotics in cancer prevention. . Cancers 13::20
    [Crossref] [Google Scholar]
  122. 122.
    Vallianou N, Stratigou T, Christodoulatos GS, Tsigalou C, Dalamaga M. 2020.. Probiotics, prebiotics, synbiotics, postbiotics, and obesity: current evidence, controversies, and perspectives. . Curr. Obes. Rep. 9::17992
    [Crossref] [Google Scholar]
  123. 123.
    Oliveira RJ, Matuo R, da Silva AF, Matiazi HJ, Mantovani MS, Ribeiro LR. 2007.. Protective effect of beta-glucan extracted from Saccharomyces cerevisiae, against DNA damage and cytotoxicity in wild-type (k1) and repair-deficient (xrs5) CHO cells. . Toxicol. In Vitro 21::4152
    [Crossref] [Google Scholar]
  124. 124.
    Chen X, Kokkotou EG, Mustafa N, Bhaskar KR, Sougioultzis S, et al. 2006.. Saccharomyces boulardii inhibits ERK1/2 mitogen-activated protein kinase activation both in vitro and in vivo and protects against Clostridium difficile toxin A-induced enteritis. . J. Biol. Chem. 281::2444954
    [Crossref] [Google Scholar]
  125. 125.
    Chen X, Yang G, Song JH, Xu H, Li D, et al. 2013.. Probiotic yeast inhibits VEGFR signaling and angiogenesis in intestinal inflammation. . PLOS ONE 8::e64227
    [Crossref] [Google Scholar]
  126. 126.
    Jahanshahi M, Maleki Dana P, Badehnoosh B, Asemi Z, Hallajzadeh J, et al. 2020.. Anti-tumor activities of probiotics in cervical cancer. . J. Ovarian Res. 13::68
    [Crossref] [Google Scholar]
  127. 127.
    Konishi H, Isozaki S, Kashima S, Moriichi K, Ichikawa S, et al. 2021.. Probiotic Aspergillus oryzae produces anti-tumor mediator and exerts anti-tumor effects in pancreatic cancer through the p38 MAPK signaling pathway. . Sci. Rep. 11::11070
    [Crossref] [Google Scholar]
  128. 128.
    Offei B, Vandecruys P, De Graeve S, Foulquie-Moreno MR, Thevelein JM. 2019.. Unique genetic basis of the distinct antibiotic potency of high acetic acid production in the probiotic yeast Saccharomyces cerevisiae var. boulardii. . Genome Res. 29::147894
    [Crossref] [Google Scholar]
  129. 129.
    Vallianou N, Stratigou T, Christodoulatos GS, Dalamaga M. 2019.. Understanding the role of the gut microbiome and microbial metabolites in obesity and obesity-associated metabolic disorders: current evidence and perspectives. . Curr. Obes. Rep. 8::31732
    [Crossref] [Google Scholar]
  130. 130.
    Haifer C, Paramsothy S, Borody TJ, Clancy A, Leong RW, Kaakoush NO. 2021.. Long-term bacterial and fungal dynamics following oral lyophilized fecal microbiota transplantation in Clostridioides difficile infection. . mSystems 6::e00905-20
    [Crossref] [Google Scholar]
  131. 131.
    Leonardi I, Paramsothy S, Doron I, Semon A, Kaakoush NO, et al. 2020.. Fungal trans-kingdom dynamics linked to responsiveness to fecal microbiota transplantation (FMT) therapy in ulcerative colitis. . Cell Host Microbe 27::82329.e3
    [Crossref] [Google Scholar]
  132. 132.
    Zuo T, Wong SH, Cheung CP, Lam K, Lui R, et al. 2018.. Gut fungal dysbiosis correlates with reduced efficacy of fecal microbiota transplantation in Clostridium difficile infection. . Nat. Commun. 9::3663
    [Crossref] [Google Scholar]
  133. 133.
    Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, et al. 2018.. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. . Science 359::9197
    [Crossref] [Google Scholar]
  134. 134.
    Sung L, Lange BJ, Gerbing RB, Alonzo TA, Feusner J. 2007.. Microbiologically documented infections and infection-related mortality in children with acute myeloid leukemia. . Blood 110::353239
    [Crossref] [Google Scholar]
  135. 135.
    Dart A. 2019.. Fungi complements cancer. . Nat. Rev. Cancer 19::665
    [Crossref] [Google Scholar]
  136. 136.
    Pantziarka P, Sukhatme V, Bouche G, Meheus L, Sukhatme VP. 2015.. Repurposing drugs in oncology (ReDO)—itraconazole as an anti-cancer agent. . Ecancermedicalscience 9::521
    [Google Scholar]
  137. 137.
    Tsubamoto H, Ueda T, Inoue K, Sakata K, Shibahara H, Sonoda T. 2017.. Repurposing itraconazole as an anticancer agent. . Oncol. Lett. 14::124046
    [Crossref] [Google Scholar]
  138. 138.
    Lockhart NR, Waddell JA, Schrock NE. 2016.. Itraconazole therapy in a pancreatic adenocarcinoma patient: a case report. . J. Oncol. Pharm. Pract. 22::52832
    [Crossref] [Google Scholar]
  139. 139.
    Sanati H, Belanger P, Fratti R, Ghannoum M. 1997.. A new triazole, voriconazole (UK-109,496), blocks sterol biosynthesis in Candida albicans and Candida krusei. . Antimicrob. Agents Chemother. 41::249296
    [Crossref] [Google Scholar]
  140. 140.
    Lehrnbecher T, Bochennek K, Klingebiel T, Gastine S, Hempel G, Groll AH. 2019.. Extended dosing regimens for fungal prophylaxis. . Clin. Microbiol. Rev. 32::e00010-19
    [Crossref] [Google Scholar]
  141. 141.
    Walsh TJ, Lee JW, Kelly P, Bacher J, Lecciones J, et al. 1991.. Antifungal effects of the nonlinear pharmacokinetics of cilofungin, a 1,3-beta-glucan synthetase inhibitor, during continuous and intermittent intravenous infusions in treatment of experimental disseminated candidiasis. . Antimicrob. Agents Chemother. 35::132128
    [Crossref] [Google Scholar]
  142. 142.
    Pfaller MA, Messer SA, Rhomberg PR, Jones RN, Castanheira M. 2016.. Activity of a long-acting echinocandin, CD101, determined using CLSI and EUCAST reference methods, against Candida and Aspergillus spp., including echinocandin- and azole-resistant isolates. . J. Antimicrob. Chemother. 71::286873
    [Crossref] [Google Scholar]
  143. 143.
    Wheeler ML, Limon JJ, Bar AS, Leal CA, Gargus M, et al. 2016.. Immunological consequences of intestinal fungal dysbiosis. . Cell Host Microbe 19::86573
    [Crossref] [Google Scholar]
  144. 144.
    Swanton C, Bernard E, Abbosh C, Andre F, Auwerx J, et al. 2024.. Embracing cancer complexity: hallmarks of systemic disease. . Cell 187::1589616
    [Crossref] [Google Scholar]
  145. 145.
    Helmink BA, Khan MAW, Hermann A, Gopalakrishnan V, Wargo JA. 2019.. The microbiome, cancer, and cancer therapy. . Nat. Med. 25::37788
    [Crossref] [Google Scholar]
  146. 146.
    Sepich-Poore GD, Zitvogel L, Straussman R, Hasty J, Wargo JA, Knight R. 2021.. The microbiome and human cancer. . Science 371:(6536):eabc4552
    [Crossref] [Google Scholar]
  147. 147.
    Frau A, Kenny JG, Lenzi L, Campbell BJ, Ijaz UZ, et al. 2019.. DNA extraction and amplicon production strategies deeply influence the outcome of gut mycobiome studies. . Sci. Rep. 9::9328
    [Crossref] [Google Scholar]
  148. 148.
    Angebault C, Ghozlane A, Volant S, Botterel F, d'Enfert C, Bougnoux ME. 2018.. Combined bacterial and fungal intestinal microbiota analyses: impact of storage conditions and DNA extraction protocols. . PLOS ONE 13::e0201174
    [Crossref] [Google Scholar]
  149. 149.
    Lücking R, Hawksworth DL. 2018.. Formal description of sequence-based voucherless Fungi: promises and pitfalls, and how to resolve them. . IMA Fungus 9::14365
    [Crossref] [Google Scholar]
  150. 150.
    Gautam AK, Verma RK, Avasthi S, Sushma, Bohra Y, et al. 2022.. Current insight into traditional and modern methods in fungal diversity estimates. . J. Fungi 8::226
    [Crossref] [Google Scholar]
  151. 151.
    Borman AM, Johnson EM. 2023.. Changes in fungal taxonomy: mycological rationale and clinical implications. . Clin. Microbiol. Rev. 36::e0009922
    [Crossref] [Google Scholar]
  152. 152.
    Lofgren LA, Uehling JK, Branco S, Bruns TD, Martin F, Kennedy PG. 2019.. Genome-based estimates of fungal rDNA copy number variation across phylogenetic scales and ecological lifestyles. . Mol. Ecol. 28::72130
    [Crossref] [Google Scholar]
  153. 153.
    Tedersoo L, Bahram M, Zinger L, Nilsson RH, Kennedy PG, et al. 2022.. Best practices in metabarcoding of fungi: from experimental design to results. . Mol. Ecol. 31::276995
    [Crossref] [Google Scholar]
  154. 154.
    Wilson AW, Eberhardt U, Nguyen N, Noffsinger CR, Swenie RA, et al. 2023.. Does one size fit all? Variations in the DNA barcode gaps of macrofungal genera. . J. Fungi 9::788
    [Crossref] [Google Scholar]
  155. 155.
    Alnuaimi AD, Ramdzan AN, Wiesenfeld D, O'Brien-Simpson NM, et al. 2016.. Candida virulence and ethanol-derived acetaldehyde production in oral cancer and non-cancer subjects. . Oral Dis. 22::80514
    [Crossref] [Google Scholar]
  156. 156.
    de Klerk N, Maudsdotter L, Gebreegziabher H, Saroj SD, Eriksson B, et al. 2016.. Lactobacilli reduce Helicobacter pylori attachment to host gastric epithelial cells by inhibiting adhesion gene expression. . Infect. Immun. 84::152635
    [Crossref] [Google Scholar]
/content/journals/10.1146/annurev-pathmechdis-111523-023524
Loading
/content/journals/10.1146/annurev-pathmechdis-111523-023524
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error