Cited by 1,375Gut microbiota and healthColorectal Cancer Screening and DetectionGenetic factors in colorectal cancer

Potential of fecal microbiota for early-stage detection of colorectal cancer

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Zeller, Georg, Tap, Julien, Voigt, Anita Y, Sunagawa, Shinichi, Kultima, Jens Roat, Costea, Paul I, Amiot, Aurélien, Böhm, Jürgen +18 more·2014·Molecular Systems Biology

Abstract

Several bacterial species have been implicated in the development of colorectal carcinoma (CRC), but CRC-associated changes of fecal microbiota and their potential for cancer screening remain to be explored. Here, we used metagenomic sequencing of fecal samples to identify taxonomic markers that distinguished CRC patients from tumor-free controls in a study population of 156 participants. Accuracy of metagenomic CRC detection was similar to the standard fecal occult blood test (FOBT) and when both approaches were combined, sensitivity improved > 45% relative to the FOBT, while maintaining its specificity. Accuracy of metagenomic CRC detection did not differ significantly between early- and late-stage cancer and could be validated in independent patient and control populations (N = 335) from different countries. CRC-associated changes in the fecal microbiome at least partially reflected microbial community composition at the tumor itself, indicating that observed gene pool differences may reveal tumor-related host-microbe interactions. Indeed, we deduced a metabolic shift from fiber degradation in controls to utilization of host carbohydrates and amino acids in CRC patients, accompanied by an increase of lipopolysaccharide metabolism.

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  • Fecal microbiome studies using 16S rRNA or shotgun metagenomic sequencing found Fusobacterium nucleatum increased in fecal samples from colorectal cancer or adenoma patients compared with controls.

    “studies of fecal microbiomes that used either 16s rRNA or shotgun metagenomic sequencing found that F nucleatum to be increased in fecal samples from patients with CRC or adenoma compared with controls (Table 1).15, 18, 35–39”
  • Salmonella's AvrA protein drives inflammation and colon tumor growth through activation of beta-catenin signaling to STAT3.

    “The protein AvrA, produced by Salmonella, promotes inflammation and colon tumor development by activating beta-catenin signaling to STAT3.36, 180”

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  1. Bernstein CN Blanchard JF Kliewer E Wajda A Cancer risk in patients with inflammatory bowel disease: a population-based study Cancer 2001 91 854 862 11241255

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Authors
Zeller, G., Tap, J., Voigt, A. Y., Sunagawa, S., Kultima, J. R., Costea, P. I., Amiot, A., Böhm, J., Brunetti, F., Habermann, N., Hercog, R., Koch, M., Luciani, A., Mende, D. R., Schneider, M. A., Schrotz‐King, P., Tournigand, C., Tran Van Nhieu, J., Yamada, T., Zimmermann, J., Benes, V., Kloor, M., Ulrich, C. M., von Knebel Doeberitz, M., Sobhani, I., & Bork, P.
Affiliations
  • European Molecular Biology Laboratory (DE)
  • Université Paris-Est Créteil (FR)
  • German Cancer Research Center (DE)
  • University Hospital Heidelberg (DE)
  • Tokyo Institute of Technology (JP)
Corresponding author
Sobhani, Iradj
Venue
Molecular Systems Biology
Published
2014-11-01
Volume
10
Issue
11
Pages
766-766
ISSN
1744-4292 (ISSN-L)
OpenAlex
W2130725058
Cited by
1,375
References
98
Citations by year
2026: 131 · 2025: 168 · 2024: 162 · 2023: 134 · 2022: 160 · 2021: 140 · 2020: 134 · 2019: 97 · 2018: 82 · 2017: 85 · 2016: 59 · 2015: 20 · 2014: 1
FWCI
22.57
Type
journal article
Language
en
Open access
Locations
  • Molecular Systems Biology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (acceptedVersion)
  • HAL (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • European Research Council (268985)
  • METACARDIS (FP7‐HEALTH‐2012‐INNOVATION‐I‐305312)
  • International Human Microbiome Standards (HEALTH‐F4‐2010‐261376)
  • French LNCC 2004 grant
  • ACD grants
  • PHRC 2009 Vatnimad grant
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Oncology › Colorectal Cancer Screening and Detection
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
Keywords
colorectal cancer, fecal microbiota, early cancer detection, cancer screening, metagenomics, fecal occult blood test, microbial biomarkers, host-microbe interactions, fiber degradation
MeSH terms
Feces, Humans, Occult Blood, Sensitivity and Specificity, Colorectal Neoplasms, Case-Control Studies, Early Detection of Cancer, Metagenomics, Molecular Typing, Microbiota

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