Abstract
Increasing evidence suggests a role of the gut microbiota in colorectal carcinogenesis (CRC). To detect bacterial markers of colorectal cancer in African Americans a metabolomic analysis was performed on fecal water extracts. DNA from stool samples of adenoma and healthy subjects and from colon cancer and matched normal tissues was analyzed to determine the microbiota composition (using 16S rDNA) and genomic content (metagenomics). Metagenomic functions with discriminative power between healthy and neoplastic specimens were established. Quantitative Polymerase Chain Reaction (q-PCR) using primers and probes specific to Streptococcus sp. VT_162 were used to validate this bacterium association with neoplastic transformation in stool samples from two independent cohorts of African Americans and Chinese patients with colorectal lesions. The metabolomic analysis of adenomas revealed low amino acids content. The microbiota in both cancer vs. normal tissues and adenoma vs. normal stool samples were different at the 16S rRNA gene level. Cross-mapping of metagenomic data led to 9 markers with significant discriminative power between normal and diseased specimens. These markers identified with Streptococcus sp. VT_162. Q-PCR data showed a statistically significant presence of this bacterium in advanced adenoma and cancer samples in an independent cohort of CRC patients. We defined metagenomic functions from Streptococcus sp. VT_162 with discriminative power among cancers vs. matched normal and adenomas vs. healthy subjects’ stools. Streptococcus sp. VT_162 specific 16S rDNA was validated in an independent cohort. These findings might facilitate non-invasive screening for colorectal cancer.
Highlights
Colorectal cancer (CRC) is the third most prevalent cancer worldwide [1,2,3]
Our present study extends those findings with the specific goal of finding gut microbiota markers with diagnostic value, taking into consideration the likely participation of several bacterial actors at once in a process as complex as cancer in the colon that harbors the most diverse microbiome in the human body
We report here the presence of distinct stool metabolomic profiles in patients with colon adenomas when compared to those from healthy subjects
Summary
Colorectal cancer (CRC) is the third most prevalent cancer worldwide [1,2,3]. It is more prevalent in the West than in other part of the World. Similar findings were obtained in colorectal cancer mouse models with enterotoxigenic Bacteroides fragilis [20,21]. Molecular analysis of the colonic luminal and mucosal microbiota indicates that individuals harbor unique microbiotas that are fairly stable along the colonic axis. The mucosal microbiota is either distinct or contains only a subset of the bacterial phylotypes identified in the luminal fecal samples [24,25]
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