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.
Every year, more than 945000 people develop colorectal cancer worldwide, and around 492000 patients die. This form of cancer develops sporadically, in the setting of hereditary cancer syndromes, or on the basis of inflammatory bowel diseases. Screening and prevention programmes are available for all these causes and should be more widely publicised. The adenoma-carcinoma sequence is the basis for development of colorectal cancer, and the underlying molecular changes have largely been identified. Prognosis depends on factors related to the patient, treatment, and tumour, and the expertise of the treatment team is one of the major determinants of outcome. New information on the molecular basis of this cancer have led to the development of targeted therapeutic options, which are being tested in clinical trials. Further clinical progress will largely depend on the broader implementation of multidisciplinary treatment strategies following the principles of evidence-based medicine.
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