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Distinct gut microbiome patterns associate with consensus molecular subtypes of colorectal cancer
Open accessPublished version of a preprint
Abstract
Colorectal cancer (CRC) is a heterogeneous disease and recent advances in subtype classification have successfully stratified the disease using molecular profiling. The contribution of bacterial species to CRC development is increasingly acknowledged, and here, we sought to analyse CRC microbiomes and relate them to tumour consensus molecular subtypes (CMS), in order to better understand the relationship between bacterial species and the molecular mechanisms associated with CRC subtypes. We classified 34 tumours into CRC subtypes using RNA-sequencing derived gene expression and determined relative abundances of bacterial taxonomic groups using 16S rRNA amplicon metabarcoding. 16S rRNA analysis showed enrichment of Fusobacteria and Bacteroidetes, and decreased levels of Firmicutes and Proteobacteria in CMS1. A more detailed analysis of bacterial taxa using non-human RNA-sequencing reads uncovered distinct bacterial communities associated with each molecular subtype. The most highly enriched species associated with CMS1 included Fusobacterium hwasookii and Porphyromonas gingivalis. CMS2 was enriched for Selenomas and Prevotella species, while CMS3 had few significant associations. Targeted quantitative PCR validated these findings and also showed an enrichment of Fusobacterium nucleatum, Parvimonas micra and Peptostreptococcus stomatis in CMS1. In this study, we have successfully associated individual bacterial species to CRC subtypes for the first time.
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“A study associated F nucleatum with the consensus molecular subtype 1 of CRC,32”
From Influence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer (2020) · cites this paper as [32]
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Priya, S., Burns, M. B., Ward, T., Mars, R. A. T., Adamowicz, E. M., Lock, E. F., Kashyap, P., Knights, D., & Blekhman, R. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.03.29.437589 · Cited by 5
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Intratumoral microbiota in cancer: molecular mechanism and therapeutic strategies
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“Porphyromonas has been identified in the digestive tract, with two primary species: P. asaccharolytica [89] and P. gingivalis [90].”
Arvelo, F. A., Sojo, F. J., & Cotte, C. (2021) · Investigación Clínica · doi:10.22209/ic.v62n4a09 · Cited by 5
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“micra has also been reported to be associated with colon cancer consensus molecular subtype 1 [28].”
BackgroundBergsten, E., Mestivier, D., Donnadieu, F., Pédron, T., Barau, C., Tsoumtsa, L. L., Mettouchi, A., Lemichez, E., Gorgette, O., Chamaillard, M., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.05.14.491935 · Cited by 4
Rethinking Colorectal Cancer Microbiome: From Universal Biomarkers to Patient-Stratified Signatures
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“…microbiomes to CMS classification, revealing that oral-associated taxa like Fn , P. gingivalis , and Porphyromonas species were more common in CMS1 tumors, while CMS2 tumors showed enrichment in Selenomonas and Prevotella species, and CMS4 tumors exhibited other unique microbial associations [46].”
Boatman, S. M., Kohn, J. F., Mott, S. L., Gaertner, W. B., Madoff, R. D., Melton, G. B., Shaukat, A., Hassan, I., & Goffredo, P. (2024) · Journal of Gastrointestinal Surgery · doi:10.1016/j.gassur.2024.02.024 · Cited by 3
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“Even though several studies have investigated CRC-associated microbiota 30–34 , very limited data exist in the context of the Ghanaian population.”
BackgroundInnate Immune Pattern Recognition and the Development of Intestinal Cancer
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Why Does a High-Fat Diet Increase Cancer Risk?
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“nucleatum, create a particular condition by recruiting T cells resembling the immunological aspects in speciic colorectal tumors [94].”
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“Although a low bacterial biomass has been associated with the CMS2 subtype of CRC, a higher proportion of B. fragilis has been observed in patients with tumors of this subtype compared to patients with other CMS subtypes [192] (Figure 2).”
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Role of the Microbiome in the Formation and Development of Colorectal Cancer
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Does Sidedness Matter in Unresectable Colorectal Cancer?
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“29 64 The genera decreased in abundance including species producing short-chain fatty acids (SFCAs), which are essential molecules that fulfil 70% of the energy needs of colonocytes, the cells lining the colon.”
Zhang, X., Sun, S., Cheng, S., Dai, J., Du, F., Wang, J., Wei, D., Yan, Y., & Liu, Y. (2025) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2025.1601688 · Cited by 1
Korobkova, L., Thornton, M. E., Collin, M. A., Morin, E. L., Aoued, H. S., Sannigrahi, S., Bhinderwala, N., Garza, K. M., Siebert, E. R., Walum, H., et al. (2025) · Biological Psychiatry · doi:10.1016/j.biopsych.2025.08.020 · Cited by 1
Michaud, D. S., Platz, E. A., Garrett, W. S., Waterboer, T., Kaaks, R., Pasanisi, F., Abilleira, E., Pala, V. M., Milani, L., Castilla, J., et al. (2025) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-25-1084 · Cited by 1
Gut Microbiota in Colorectal Cancer Carcinogenesis: The Evolution of Hypotheses
Glazunova, E. V., Kurnosov, A., Molodtsova, P. A., Moskalenko, A. M., Makarov, V. V., & Zlobovskaya, O. A. (2025) · Molecular Biology · doi:10.1134/s0026893325700335 · Cited by 1
“Less common are some other molecular pathways that lead to CRC [13, 25].”
InfluentialInterplay Between Gut Microbiota and Cholesterol Metabolism in Colorectal Cancer
Li, S. W., Au, O. T. H., Lau, E. Y. T., Lu, R. Y., Zaleski, A. L., & Liang, Q. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27062553 · Cited by 1
“Distinct gut microbiome patterns have been associated with CMSs, such as F . nucleatum enrichment in CMS1 and CMS3 [115,116].”
The gut microbiome and colorectal cancer
Dietz, M. A., Subramanian, S., & Staley, C. M. (2026) · Clinical Microbiology Reviews · doi:10.1128/cmr.00332-25 · Cited by 1
“Additionally, distinct subtypes of CRC have been found to have distinct microbial compositions within their TME, indicating that the tumor-microbe relationship may differ based on CRC subtype (276).”
Cross-study analyses of microbial abundance using generalized common factor methods
Hayes, M. G., Langille, M. G. I., & Gu, H. (2023) · BMC Bioinformatics · doi:10.1186/s12859-023-05509-4 · Cited by 1
“Genera we identified that have been previously associated with CRC in additional studies include Fusobacterium (Purcell et al., 2017; Chen et al., 2012), Porphorymonas (Purcell et al.”
ResultInfluentialTheodoropoulos, G. E. (2021) · The microbiomes of humans, animals, plants, and the environment · doi:10.1007/978-3-030-59642-2_4 · Cited by 1
Boatman, S. M., Kohn, J. F., Mott, S. L., Marmor, S., Madoff, R. D., Gaertner, W. B., Shaukat, A., Melton, G. B., Hassan, I., & Goffredo, P. (2023) · Techniques and Innovations in Gastrointestinal Endoscopy · doi:10.1016/j.tige.2023.07.003 · Cited by 1
The influence of gut microbiota on immunotherapy for Colorectal Cancer
de Melo, F. F. (2023) · Gastrointestinal Tract · doi:10.54844/git.2023.421 · Cited by 1
Metadata
- Authors
- Purcell, R. V., Visnovska, M., Biggs, P. J., Schmeier, S., & Frizelle, F. A.
- Affiliations
- University of Otago (NZ)
- Massey University (NZ)
- Corresponding author
- Purcell, Rachel V.
- Venue
- Scientific Reports
- Published
- 2017-09-14
- Volume
- 7
- Issue
- 1
- Pages
- 11590-11590
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5599497
- OpenAlex
- W2950036522
- Cited by
- 227
- References
- 60
- Citations by year
- 2026: 16 · 2025: 24 · 2024: 21 · 2023: 34 · 2022: 33 · 2021: 40 · 2020: 20 · 2019: 21 · 2018: 17
- FWCI
- 6.48
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Hugh Green Foundation
- Maurice and Phyllis Paykel Trust
- Colorectal Surgical Society of Australia and New Zealand
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Keywords
- colorectal cancer, gut microbiota, consensus molecular subtypes, Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella, bacterial taxa, tumor molecular subtypes, 16S rRNA metabarcoding
- MeSH terms
- Gastrointestinal Microbiome, Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, RNA, Ribosomal, 16S, Biomarkers, Tumor, Colorectal Neoplasms, Reproducibility of Results, Gene Expression Regulation, Neoplastic, Computational Biology, Gene Expression Profiling, Metagenome, Metagenomics, Transcriptome
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