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Distinct gut microbiome patterns associate with consensus molecular subtypes of colorectal cancer
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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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“On the other hand, CRC microbiomes might be associated CMS, for example, elevated abundance of Fusobacterium, Peptostreptococcus, or Parvimonas, to be associated with CMS1, underscored the potential role of oral poly-microbial communities in the development of a subset of CRC pathogenesis (Purcell et al. 2017).”
BackgroundHARMONIES: A Hybrid Approach for Microbiome Networks Inference via Exploiting Sparsity
Jiang, S., Xiao, G., Koh, A. Y., Chen, Y., Yao, B., Li, Q., & Zhan, X. (2020) · Frontiers in Genetics · doi:10.3389/fgene.2020.00445 · Cited by 36
Association of the microbiome with colorectal cancer development (Review)
Abdulla, M., Agarwal, D., Singh, J. K., Traiki, T. A. B., Pandey, M. K., Ahmad, R., & Srivastava, S. K. (2021) · International Journal of Oncology · doi:10.3892/ijo.2021.5197 · Cited by 34
Current status and future perspective of immune checkpoint inhibitors in colorectal cancer
Zhou, C., Cheng, X., & Tu, S. (2021) · Cancer Letters · doi:10.1016/j.canlet.2021.07.023 · Cited by 35
The human microbiome and genitourinary malignancies
Nicolaro, M., Portal, D. E., Shinder, B. M., Patel, H. V., & Singer, E. A. (2020) · Annals of Translational Medicine · doi:10.21037/atm-20-2976 · Cited by 31
“pathological processes such as aging, atherosclerosis, obesity, diabetes, CNS dysfunction, and even malignancies such as colorectal cancers (6-8).”
BackgroundQueen, J., Shaikh, F. Y., & Sears, C. L. (2023) · Nature Cancer · doi:10.1038/s43018-023-00602-2 · Cited by 34
Gut Microbiome–Colorectal Cancer Relationship
Yadav, D., Sainatham, C., Filippov, E., Kanagala, S. G., Ishaq, S. M., & Jayakrishnan, T. (2024) · Microorganisms · doi:10.3390/microorganisms12030484 · Cited by 33
“…, Peptostreptococcus spp, Solobacterium moorei , Clostridium symbiosum , Anaerococcus spp, Porphyromonas spp, Prevotella intermedia , Bacteroides fragilis , Streptococcus constellatus , Granuclicatella adiacens , Treponema denticola , Porphyromonas gingivalis and Tannerrella forsthica [24,25,70].”
BackgroundApplying artificial intelligence in the microbiome for gastrointestinal diseases: A review
Zeng, T., Yu, X., & Chen, Z. (2021) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.15503 · Cited by 30
“28 Second, the gene-targeted amplicons and metagenomics big data could support the integration of novel microbiome signatures.”
BackgroundA New Comorbidity in Periodontitis: Fusobacterium nucleatum and Colorectal Cancer
Mesa, F., Mesa-López, M. J., VALENZUELA, J. E., Benavides‐Reyes, C., Nibali, L., Ide, M., Mainas, G., Rizzo, M., & Magán‐Fernández, A. (2022) · Medicina · doi:10.3390/medicina58040546 · Cited by 34
“This finding reaffirms the theory of the role played by the oral microbiome in the development of CRC [55], together with the fact that 40% of the patients showed identical Fn strains in CRC samples and in saliva samples [56].”
ResultDistinct changes in the colonic microbiome associated with acute diverticulitis
O’Grady, M. J., Turner, G. A., Sulit, A. K., Frizelle, F., & Purcell, R. V. (2022) · Colorectal Disease · doi:10.1111/codi.16271 · Cited by 30
“abundance was Fusobacterium, which is correlated with the pathogenesis of colorectal cancer through activation of host inflammatory responses [25, 42].”
BackgroundAn epigenetic signature of advanced colorectal cancer metastasis
Rodger, E. J., Gimenez, G., Ajithkumar, P., Stockwell, P. A., Almomani, S. N., Bowden, S. A., Leichter, A. L., Ahn, A., Pattison, S. T., McCall, J. L., et al. (2023) · iScience · doi:10.1016/j.isci.2023.106986 · Cited by 32
Higashi, D. L., Krieger, M., Qin, H., Zou, Z., Palmer, E. A., Kreth, J., & Merritt, J. L. (2023) · Environmental Microbiology Reports · doi:10.1111/1758-2229.13153 · Cited by 29
“It has been suggested that P. micra exhibits the strongest correlation with consensus molecular subtype 1 CRC (Purcell et al., 2017).”
BackgroundInfluentialThe role of microbiomes in gastrointestinal cancers: new insights
Yarahmadi, A., & Afkhami, H. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2023.1344328 · Cited by 30
Löwenmark, T., Li, X., Löfgren‐Burström, A., Zingmark, C., Ling, A., Kellgren, T. G., Larsson, P. G., Ljuslinder, I., Wai, S. N., Edin, S., et al. (2022) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-022-03179-4 · Cited by 29
Jin, M., Wu, J., Shi, L., Zhou, B., Shang, F., Chang, X., Dong, X., Deng, S., Liu, L., Cai, K., et al. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.993285 · Cited by 29
“found that certain gut microbiome patterns including Fusobacterium hwasookii and Porphyromonas gingivalis enrichment is associated with the CMS 1 subtype in CRC (Purcell et al., 2017).”
BackgroundLöwenmark, T., Löfgren‐Burström, A., Zingmark, C., Ljuslinder, I., Dahlberg, M. L., Edin, S., & Palmqvist, R. (2022) · Cancers · doi:10.3390/cancers14235937 · Cited by 30
“nucleatum in tumour tissue and tumours of CMS subgroup 1 were found [22,25].”
BackgroundAja‐Macaya, P., Conde‐Pérez, K., Trigo‐Tasende, N., Buetas, E., Nasser‐Ali, M., Nión, P., Rumbo‐Feal, S., Ladra, S., Bou, G., Mira, Á., et al. (2025) · Scientific Reports · doi:10.1038/s41598-025-10999-8 · Cited by 35
Sheikh, A. A., Taube, J. H., & Greathouse, K. L. (2021) · Carcinogenesis · doi:10.1093/carcin/bgab060 · Cited by 26
Gut microbiota in colorectal cancer: From pathogenesis to clinic
Fusco, W., Bricca, L., Kaitsas, F., Tartaglia, M., Venturini, I., Rugge, M., Gasbarrini, A., Cammarota, G., & Ianiro, G. (2024) · Best Practice & Research Clinical Gastroenterology · doi:10.1016/j.bpg.2024.101941 · Cited by 32
Hawkins, G. M., Burkett, W. C., McCoy, A. N., Nichols, H. B., Olshan, A. F., Broaddus, R. R., Merker, J. D., Weissman, B. E., Brewster, W. R., Roach, J. M., et al. (2022) · Gynecologic Oncology · doi:10.1016/j.ygyno.2022.02.021 · Cited by 27
Mohammadi, M., Mirzaei, H., & Motallebi, M. (2021) · Anaerobe · doi:10.1016/j.anaerobe.2021.102501 · Cited by 26
Small-molecule drugs of colorectal cancer: Current status and future directions
Yang, Y., Liu, P., Zhou, M., Yin, L., Wang, M., Liu, T., Jiang, X., & Gao, H. (2023) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2023.166880 · Cited by 27
Kim, M., Lee, S., Choi, S., Lee, H., Kwon, S. S., Byun, J., Kim, Y. A., Rhee, K., Choi, J. R., Kim, T. I., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-76467-7 · Cited by 25
Implication of gut microbes and its metabolites in colorectal cancer
Kumar, A., Ali, A., Kapardar, R. K., Dar, G. M., Nimisha, Apurva, A., Sharma, A. K., Verma, R., Sattar, R. S. A., Ahmad, E., et al. (2022) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-022-04422-2 · Cited by 26
Wielandt, A. M., Hurtado, C., Mauricio Moreno, C., Villarroel, C., Castro, M., Estay, M., Simian, D., Martínez, M., Vial, M. T., Kronberg, U., et al. (2020) · Tumor Biology · doi:10.1177/1010428320938492 · Cited by 24
Drug–Microbiota Interaction in Colon Cancer Therapy: Impact of Antibiotics
Mohamed, A. A., Menon, H., Chulkina, M., Yee, N. S., & Pinchuk, I. V. (2021) · Biomedicines · doi:10.3390/biomedicines9030259 · Cited by 27
Microbiome in drug resistance to colon cancer
Pandey, K. R., & Umar, S. (2021) · Current Opinion in Physiology · doi:10.1016/j.cophys.2021.100472 · Cited by 24
Oral pathogen in the pathogenesis of colorectal cancer
Yu, T., Zhou, Y., & Fang, J. (2021) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.15743 · Cited by 25
Altered Gut Microbiota Associated With Hemorrhage in Chronic Radiation Proctitis
Liu, L., Chen, C., Chen, C., Chen, B., Xiao, N., & Liang, J. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.637265 · Cited by 23
Serrated neoplasia in the colorectum: gut microbiota and molecular pathways
Kang, X., Zhang, R., Kwong, T. N. Y., Lui, R. N.-S., Wu, W. K. K., Sung, J. J. �., Yu, J. Q., & Wong, S. H. (2020) · Gut Microbes · doi:10.1080/19490976.2020.1863135 · Cited by 23
DeepLINK: Deep learning inference using knockoffs with applications to genomics
Zhu, Z., Fan, Y., Kong, Y., Lv, J., & Sun, F. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2104683118 · Cited by 23
The Gut Microbiome, Microsatellite Status and the Response to Immunotherapy in Colorectal Cancer
Sillo, T. O., Beggs, A. D., Middleton, G., & Akingboye, A. A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065767 · Cited by 25
“These differences in the gut microbiome profile also extend to different molecular and genomic subtypes of CRC [18,19].”
BackgroundMethodRemodelling of colorectal cancer cell signalling by microbiota and immunity in diabetes
Gutiérrez‐Salmerón, M. T., Lucena, S. R., Chocarro‐Calvo, A., García-Martínez, J. M., Orozco, R. M. M., & García‐Jiménez, C. (2021) · Endocrine Related Cancer · doi:10.1530/erc-20-0315 · Cited by 22
Ros, J., Baraibar, I., Martini, G., Salvà, F., Gonzalez, N. S., Cuadra‐Urteaga, J. L., Dienstmann, R., Tabernero, J. M., & Élez, E. (2021) · Current Treatment Options in Oncology · doi:10.1007/s11864-021-00913-5 · Cited by 22
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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