Leveraging sequence-based faecal microbial community survey data to identify a composite biomarker for colorectal cancer
Abstract
OBJECTIVE: Colorectal cancer (CRC) is the second leading cause of cancer-associated mortality in the USA. The faecal microbiome may provide non-invasive biomarkers of CRC and indicate transition in the adenoma-carcinoma sequence. Re-analysing raw sequence and metadata from several studies uniformly, we sought to identify a composite and generalisable microbial marker for CRC. DESIGN: Raw 16S rRNA gene sequence data sets from nine studies were processed with two pipelines, (1) QIIME closed reference (QIIME-CR) or (2) a strain-specific method herein termed SS-UP (Strain Select, UPARSE bioinformatics pipeline). A total of 509 samples (79 colorectal adenoma, 195 CRC and 235 controls) were analysed. Differential abundance, meta-analysis random effects regression and machine learning analyses were carried out to determine the consistency and diagnostic capabilities of potential microbial biomarkers. RESULTS: and yet-to-be-cultured members of Proteobacteria, were frequently and significantly increased in stools from patients with CRC compared with controls across studies and had high discriminatory capacity in diagnostic classification. Microbiome-based CRC versus control classification produced an area under receiver operator characteristic (AUROC) curve of 76.6% in QIIME-CR and 80.3% in SS-UP. Combining clinical and microbiome markers gave a diagnostic AUROC of 83.3% for QIIME-CR and 91.3% for SS-UP. CONCLUSIONS: Despite technological differences across studies and methods, key microbial markers emerged as important in classifying CRC cases and such could be used in a universal diagnostic for the disease. The choice of bioinformatics pipeline influenced accuracy of classification. Strain-resolved microbial markers might prove crucial in providing a microbial diagnostic for CRC.
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Besides Fusobacterium, other oral bacteria and periodontal disease markers are enriched in colorectal tumors and feces, including Porphyromonas, Peptostreptococcus, and Parvimonas micra.
“Besides Fusobacterium, other oral bacteria and markers of periodontal disease are enriched in colorectal tumors and feces of patients, including the genera of Porphyromonas and Peptostreptococcus, and Parvimonas micra.15, 35, 37, 38, 53”
From Influence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer (2020) · cites this paper as [53]
Compared with controls, colorectal cancer patients had lower abundances of Bifidobacterium and Lactobacillus spp. and other short-chain fatty acid-producing bacteria such as Clostridium, Roseburia, Lachnospiraceae, and Faecalibacterium prausnitzii.
“several studies have shown that compared with controls, patients with CRC had lower abundances of Bifidobacterium and Lactobacillus spp,16, 18 and other SCFA-producing bacteria, such as the genera Clostridium and Roseburia, the family Lachnospiraceae, and Faecalibacterium prausnitzii.15, 35, 37, 45, 53, 129”
From Influence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer (2020) · cites this paper as [53]
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- Authors
- Shah, M. S., DeSantis, T. Z., Weinmaier, T., McMurdie, P. J., Cope, J. L., Altrichter, A., Yamal, J.-M., & Hollister, E. B.
- Affiliations
- Baylor College of Medicine (US)
- Second Genome (United States) (US)
- Department of Epidemiology, University of Texas School of Public Health, Houston, Texas, USA
- Corresponding author
- Shah, Manasi S
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2017-03-24
- Volume
- 67
- Issue
- 5
- Pages
- 882-891
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- OpenAlex
- W4254583012
- Cited by
- 180
- References
- 42
- Citations by year
- 2026: 8 · 2025: 14 · 2024: 14 · 2023: 29 · 2022: 23 · 2021: 18 · 2020: 33 · 2019: 18 · 2018: 18 · 2017: 5
- FWCI
- 1.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Gut (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Oncology › Colorectal Cancer Screening and Detection
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Bacterial Identification and Susceptibility Testing
- Keywords
- colorectal cancer, fecal microbiota, microbial biomarkers, 16S rRNA gene sequencing, Proteobacteria, colorectal adenoma, adenoma-carcinoma sequence, cancer diagnosis, bioinformatics pipeline comparison
- MeSH terms
- Gastrointestinal Microbiome, DNA, Bacterial, Feces, Humans, Surveys and Questionnaires, RNA, Ribosomal, 16S, Sensitivity and Specificity, Biomarkers, Tumor, Colorectal Neoplasms, Area Under Curve
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