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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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ResultMicrobiota disbiosis is associated with colorectal cancer
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Fusobacterium nucleatum in colorectal carcinoma tissue according to tumor location
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“biofilms in extra-intestinal infections facilitates synergistic pathogenicity[51, 52], and the high enrichment of these bacteria in CMS1 suggests that similar community synergy may be occurring in the tumour microenvironment.”
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ResultVirulence genes are a signature of the microbiome in the colorectal tumor microenvironment
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“gingivalis is also a known biofilm former that co-aggregates with Treponema denticola and Tannerrella forsythia[49, 50], both of which also show enrichment in CMS1.”
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“gene array data[34, 35], most published studies reporting of CMS classification have used expression data from the cohorts used in the initial study.”
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“was associated with a CRC subtype characterised by CpG island methylation, MSI and inflammatory signatures[15], and higher prevalence in right-sided tumours[46], all hallmarks of CMS1[6].”
BackgroundT reponema denticola improves adhesive capacities of P orphyromonas gingivalis
Meuric, V., Martin, B., Guyodo, H., Rouillon, A., Tamanai‐Shacoori, Z., Barloy-Hubler, F., & Bonnaure‐Mallet, M. (2012) · Molecular Oral Microbiology · doi:10.1111/omi.12004 · Cited by 40 · cited 1×
“gingivalis is also a known biofilm former that co-aggregates with Treponema denticola and Tannerrella forsythia[49, 50], both of which also show enrichment in CMS1.”
BackgroundPurcell, R. V., Pearson, J. F., Frizelle, F., & Keenan, J. I. (2016) · Scientific Reports · doi:10.1038/srep34554 · Cited by 34 · cited 1×
“(PGT)[26] were simultaneously measured from genomic DNA extracted from CRC tumour samples, using qPCR on a LightCycler®480 thermocycler (Roche Diagnostics, Indianapolis, IN, USA), as previously described[27].”
MethodFusobacterium hwasookii sp. nov., Isolated from a Human Periodontitis Lesion
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“nucleatum[45], was one of the bacterial species most strongly associated with CMS1 in our cohort.”
BackgroundBurns, M. B., Montassier, E., Abrahante, J., Priya, S., Niccum, D. E., Khoruts, A., Starr, T. K., Knights, D., & Blekhman, R. (2016) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/090795 · Cited by 7 · cited 2×
“Although bacterial dysbiosis, as shown through 16S rRNA and metagenomics studies, have previously been associated with CRC compared to controls[9, 10, 36, 37], and a recent study by Burns et al[14] has linked microbial composition with loss-of-function mutations in tumours, this is the first time that different bacter…”
BackgroundResult
Cited by
Sorted by citations
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“) (Feng et al., 2015; Purcell et al., 2017).”
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“Interestingly, distinct gut microbiome species are associated with CMS of colorectal cancer; thus, the most highly-enriched microbial species associated with CSM1 included Fusobacterium hwasookii and Porphyromanas gingivalis; and CMS2 was enriched for Selemonas and Prevotella species, while CMS3 had few significant as…”
BackgroundThe gut microbial metabolite formate exacerbates colorectal cancer progression
Ternes, D., Tsenkova, M., Pozdeev, V. I., Meyers, M., Koncina, E., Atatri, S., Schmitz, M., Karta, J., Schmoetten, M., Heinken, A., et al. (2022) · Nature Metabolism · doi:10.1038/s42255-022-00558-0 · Cited by 339
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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