Multi-kingdom microbiota analyses identify bacterial–fungal interactions and biomarkers of colorectal cancer across cohorts
Open accessAbstract
Despite recent progress in our understanding of the association between the gut microbiome and colorectal cancer (CRC), multi-kingdom gut microbiome dysbiosis in CRC across cohorts is unexplored. We investigated four-kingdom microbiota alterations using CRC metagenomic datasets of 1,368 samples from 8 distinct geographical cohorts. Integrated analysis identified 20 archaeal, 27 bacterial, 20 fungal and 21 viral species for each single-kingdom diagnostic model. However, our data revealed superior diagnostic accuracy for models constructed with multi-kingdom markers, in particular the addition of fungal species. Specifically, 16 multi-kingdom markers including 11 bacterial, 4 fungal and 1 archaeal feature, achieved good performance in diagnosing patients with CRC (area under the receiver operating characteristic curve (AUROC) = 0.83) and maintained accuracy across 3 independent cohorts. Coabundance analysis of the ecological network revealed associations between bacterial and fungal species, such as Talaromyces islandicus and Clostridium saccharobutylicum . Using metagenome shotgun sequencing data, the predictive power of the microbial functional potential was explored and elevated D-amino acid metabolism and butanoate metabolism were observed in CRC. Interestingly, the diagnostic model based on functional EggNOG genes achieved high accuracy (AUROC = 0.86). Collectively, our findings uncovered CRC-associated microbiota common across cohorts and demonstrate the applicability of multi-kingdom and functional markers as CRC diagnostic tools and, potentially, as therapeutic targets for the treatment of CRC.
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Studies discovered specific virome and mycobiome signatures for CRC GOMS, and in vitro and in vivo experiments showed Aspergillus rambellii can promote CRC cell growth.
“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 [87]
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Self-citation
- Authors
- Liu, N.-N., Jiao, N., Tan, J.-C., Wang, Z., Wu, D., Wang, A.-J., Chen, J., Tao, L., Zhou, C., Fang, W., Cheong, I. H., Pan, W., Liao, W., Kozlakidis, Z., Heeschen, C., Moore, G. G., Zhu, L., Chen, X., Zhang, G., Zhu, R., & Wang, H.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Sun Yat-sen University (CN)
- Shanghai University of Traditional Chinese Medicine (CN)
- Tongji University (CN)
- Chinese Academy of Sciences (CN)
- Second Military Medical University (CN)
- Centre international de recherche sur le cancer (FR)
- Agricultural Research Service (US)
- Fudan University (CN)
- Corresponding author
- Zhu, Lixin
- Chen, Xingdong
- Zhang, Guoqing
- Zhu, Ruixin
- Wang, Hui
- ORCID
- Venue
- Nature Microbiology
- Published
- 2022-01-27
- Volume
- 7
- Issue
- 2
- Pages
- 238-250
- ISSN
- 2058-5276 (ISSN-L)
- PMC
- PMC8813618
- OpenAlex
- W4210569788
- Cited by
- 306
- References
- 51
- Citations by year
- 2026: 69 · 2025: 76 · 2024: 78 · 2023: 64 · 2022: 19
- FWCI
- 20.80
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Nature Microbiology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (31900129)
- China Postdoctoral Science Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Infectious Diseases › Clostridium difficile and Clostridium perfringens research
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Keywords
- colorectal cancer, gut microbiota, fungal-bacterial interactions, fungal biomarkers, archaea, viral markers, cancer diagnosis, diagnostic biomarkers, co-occurrence networks, Talaromyces islandicus, Clostridium saccharobutylicum, D-amino acid metabolism, butanoate metabolism, functional metagenomics, cross-cohort validation
- MeSH terms
- Gastrointestinal Microbiome, Adult, Aged, Bacteria, Feces, Female, Fungi, Humans, Male, Middle Aged, Viruses, Colorectal Neoplasms, Cohort Studies, Biomarkers, Sequence Analysis, DNA, Metabolic Networks and Pathways, Metagenome, Microbial Interactions, Dysbiosis
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