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Altered Mycobiota Signatures and Enriched Pathogenic Aspergillus rambellii Are Associated With Colorectal Cancer Based on Multicohort Fecal Metagenomic Analyses
Open accessAbstract
BACKGROUND & AIMS: The enteric mycobiota is a major component of the human gut microbiota, but its role in colorectal cancer (CRC) remains largely elusive. We conducted a meta-analysis to uncover the contribution of the fungal mycobiota to CRC. METHODS: We retrieved fecal metagenomic data sets from 7 previous publications and established an additional in-house cohort, totaling 1329 metagenomes (454 with CRC, 350 with adenoma, and 525 healthy individuals). Mycobiota composition and microbial interactions were analyzed. Candidate CRC-enriched fungal species (Aspergillus rambellii) was functionally validated in vitro and in vivo. RESULTS: Multicohort analysis revealed that the enteric mycobiota was altered in CRC. We identified fungi that were associated with patients with CRC or adenoma from multiple cohorts. Signature CRC-associated fungi included 6 enriched (A rambellii, Cordyceps sp. RAO-2017, Erysiphe pulchra, Moniliophthora perniciosa, Sphaerulina musiva, and Phytophthora capsici) and 1 depleted species (A kawachii). Co-occurrent interactions among CRC-enriched fungi became stronger in CRC compared with adenoma and healthy individuals. Moreover, we reported the transkingdom interactions between enteric fungi and bacteria in CRC progression, of which A rambellii was closely associated with CRC-enriched bacteria Fusobacterium nucleatum. A rambellii promoted CRC cell growth in vitro and tumor growth in xenograft mice. We further identified that combined fungal and bacterial biomarkers were more accurate than panels with pure bacterial species to discriminate patients with CRC from healthy individuals (the area under the curve relative change increased by 1.44%-10.60%). CONCLUSIONS: This study reveals enteric mycobiota signatures and pathogenic fungi in stages of colorectal tumorigenesis. Fecal fungi can be used, in addition to bacteria, for noninvasive diagnosis of patients with CRC.
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“Studies have discovered specific virome79 and mycobiome86,87 signatures for CRC GOMS, and included in vitro and in vivo experiments showing that the fungus Aspergillus rambellii can promote CRC cell growth86.”
From Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy (2023) · cites this paper as [86]
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Metadata
- Authors
- Lin, Y., Lau, H. C.-H., Liu, Y., Kang, X., Wang, Y., Ting, N. L.-N., Kwong, T. N.-Y., Han, J., Liu, W., Liu, C., She, J., Wong, S. H., Sung, J. J.-Y., & Yu, J.
- Affiliations
- Chinese University of Hong Kong (HK)
- First Affiliated Hospital of Xi'an Jiaotong University (CN)
- Nanyang Technological University (SG)
- Corresponding author
- Yu, Jun
- ORCID
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2022-10
- Volume
- 163
- Issue
- 4
- Pages
- 908-921
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W4283075856
- Cited by
- 142
- References
- 38
- Citations by year
- 2026: 27 · 2025: 41 · 2024: 29 · 2023: 41 · 2022: 4
- FWCI
- 2.99
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Gastroenterology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DR-NTU (Nanyang Technological University) (submittedVersion, cc-by-nc-nd)
- Funders
- The Chinese University of Hong Kong
- National Key Research and Development Program of China (2020YFA0509200/2020YFA0509203)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Mycorrhizal Fungi and Plant Interactions
- Keywords
- colorectal cancer, colorectal adenoma, Fusobacterium nucleatum, fungal-bacterial interactions, colorectal carcinogenesis, non-invasive diagnosis, fecal biomarkers, Cordyceps, Moniliophthora perniciosa, Phytophthora capsici, Aspergillus kawachii
- MeSH terms
- Adenoma, Animals, Aspergillus, Bacteria, Cell Transformation, Neoplastic, Feces, Humans, Colorectal Neoplasms, Biomarkers, Mice, Metagenome
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