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

• Published in: Molecular systems biology 2014-11, Vol.10 (11), p.766-n/a
• Main Authors: Zeller, Georg, Tap, Julien, Voigt, Anita Y, Sunagawa, Shinichi, Kultima, Jens Roat, Costea, Paul I, Amiot, Aurélien, Böhm, Jürgen, Brunetti, Francesco, Habermann, Nina, Hercog, Rajna, Koch, Moritz, Luciani, Alain, Mende, Daniel R, Schneider, Martin A, Schrotz‐King, Petra, Tournigand, Christophe, Tran Van Nhieu, Jeanne, Yamada, Takuji, Zimmermann, Jürgen, Benes, Vladimir, Kloor, Matthias, Ulrich, Cornelia M, von Knebel Doeberitz, Magnus, Sobhani, Iradj, Bork, Peer
• Format: Article
• Language: English
• Subjects: Amino acids; Biodegradation; Cancer; Cancer screening; Carbohydrates; Case-Control Studies; Colonoscopy; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - diagnosis; Colorectal Neoplasms - microbiology; Community composition; Datasets; Digestive system; DNA damage; Early Detection of Cancer - methods; EMBO03; EMBO42; fecal biomarkers; Fecal microflora; Feces; Feces - microbiology; Gene pool; Genomes; human gut microbiome; Humans; Life Sciences; Lipopolysaccharides; metagenomics; Metagenomics - methods; Microbiology and Parasitology; Microbiomes; Microbiota; Microorganisms; Molecular Typing; Occult Blood; Patients; Population studies; Sensitivity and Specificity; Studies; Tumors
• ISSN: 1744-4292; 1744-4292
• DOI: 10.15252/msb.20145645

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. Synopsis Metagenomic profiling of fecal samples from colorectal cancer (CRC) patients in comparison with tumor‐free controls reveals strong associations between the gut microbiota and cancer. Their potential for noninvasive cancer screening is explored systematically. A classification model based on gut microbial marker species distinguishes CRC patients from controls with similar accuracy as the fecal occult blood test (FOBT), routinely used for clinical screening. Combining metagenomic data with the FOBT leads to a relative improvement in sensitivity of > 45% over the FOBT alone at identical specificity. Detection accuracy of the metagenomic test is maintained in an independent study population and is still high for alternative microbiome readouts, such as the abundance of 16S rRNA OTUs or families of functionally related genes. Functional metagenomic analysis indicates an increased potential of CRC‐associated microbiota for degradation of host glycans and amino acids and for pro‐inflammatory lipopolysaccharide metabolism. Graphical Abstract Metagenomic profiling of fecal samples from colorectal cancer (CRC) patients in comparison with tumor‐free controls reveals strong associations between the gut microbiota and cancer. T