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Original article
Enteric fungal microbiota dysbiosis and ecological alterations in colorectal cancer
  1. Olabisi Oluwabukola Coker1,
  2. Geicho Nakatsu1,
  3. Rudin Zhenwei Dai1,
  4. William Ka Kei Wu1,2,
  5. Sunny Hei Wong1,
  6. Siew Chien Ng1,
  7. Francis Ka Leung Chan1,
  8. Joseph Jao Yiu Sung1,
  9. Jun Yu1
  1. 1 State Key Laboratory of Digestive Disease, Department of Medicine and Therapeutics, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong
  2. 2 Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong
  1. Correspondence to Dr Jun Yu, Department of Medicine and Therapeutics, Prince of Wales Hospital, the Chinese University of Hong Kong, Shatin, Hong Kong; junyu{at}cuhk.edu.hk

Abstract

Objectives Bacteriome and virome alterations are associated with colorectal cancer (CRC). Nevertheless, the gut fungal microbiota in CRC remains largely unexplored. We aimed to characterise enteric mycobiome in CRC.

Design Faecal shotgun metagenomic sequences of 184 patients with CRC, 197 patients with adenoma and 204 control subjects from Hong Kong were analysed (discovery cohort: 73 patients with CRC and 92 control subjects; validation cohort: 111 patients with CRC, 197 patients with adenoma and 112 controls from Hong Kong). CRC-associated fungal markers and ecological changes were also validated in additional independent cohorts of 90 patients with CRC, 42 patients with adenoma and 66 control subjects of published repository sequences from Germany and France. Assignment of taxonomies was performed by exact k-mer alignment against an integrated microbial reference genome database.

Results Principal component analysis revealed separate clusters for CRC and control (p<0.0001), with distinct mycobiomes in early-stage and late-stage CRC (p=0.0048). Basidiomycota:Ascomycota ratio was higher in CRC (p=0.0042), with increase in Malasseziomycetes (p<0.0001) and decrease in Saccharomycetes (p<0.0001) and Pneumocystidomycetes (p=0.0017). Abundances of 14 fungal biomarkers distinguished CRC from controls with an area under the receiver-operating characteristic curve (AUC) of 0.93 and validated AUCs of 0.82 and 0.74 in independent Chinese cohort V1 and European cohort V2, respectively. Further ecological analysis revealed higher numbers of co-occurring fungal intrakingdom and co-exclusive bacterial–fungal correlations in CRC (p<0.0001). Moreover, co-occurrence interactions between fungi and bacteria, mostly contributed by fungal Ascomycota and bacterial Proteobacteria in control, were reverted to co-exclusive interplay in CRC (p=0.00045).

Conclusions This study revealed CRC-associated mycobiome dysbiosis characterised by altered fungal composition and ecology, signifying that the gut mycobiome might play a role in CRC.

  • colorectal cancer
  • fungi
  • gut microbiota
  • pathogen

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Footnotes

  • Contributors OOC analysed data and drafted the manuscript. GN and RZD organised and analysed data. WKKW, SHW, SCN, FKLC and JJYS commented on the study and revised the manuscript. JY designed, supervised the study and wrote the paper.

  • Funding This project was supported by Science and Technology Program Grant Shenzhen (JCYJ20170413161534162), HMRF Hong Kong (17160862), grant from Faculty of Medicine CUHK on Microbiota Research, RGC-GRF Hong Kong (14106415, 14111216, 14163817), Vice-Chancellor’s Discretionary Fund CUHK and CUHK direct grant, Shenzhen Virtual University Park Support Scheme to CUHK Shenzhen Research Institute.

  • Competing interests None declared.

  • Patient consent Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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