Characterization of the consensus mucosal microbiome of colorectal cancer

Abstract

Recent evidence suggests that dysbiosis, an imbalance of microbiota, is associated with increased risk of colorectal cancer. Diverse microbial organisms are physically associated with the cells found in tumor biopsies. Characterizing this mucosa-associated microbiome through genome sequencing has advantages compared to culture-based profiling. However, there are notable challenges in accurately characterizing the features of tumor microbiomes with methods like transcriptome sequencing. Most sequence reads originate from the host. Moreover, there is a high likelihood of bacterial contaminants being introduced. Another major challenge is the microbiome diversity among different studies. Colorectal tumors demonstrate a significant extent of microbiome variation among individuals from different geographic and ethnic origins. To address these challenges, we identified a consensus microbiome for colorectal cancer through analyzing 924 tumors from eight independent RNA-Seq data sets. A standardized meta-transcriptomic analysis pipeline was established and applied to the complete CRC cohort. Common contaminants were filtered out. Our study involved taxonomic investigation of non-human sequences, linked microbial signatures to phenotypes and the association of microbiome with tumor microenvironment components. Microbiome profiles across different CRC cohorts were compared, and recurrently altered microbial shifts specific to CRC were determined. We identified cancer-specific set of 114 microbial species associated with tumors that were found among all investigated studies. Validating our approach, we found that Fusobacterium nucleatum was one of the most enriched bacterial species in CRC. Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria were among the four most abundant phyla for CRC microbiome. Signficant associations between the consensus species and specific immune cell types were noted. Our results are available as a web data resource for other researchers to explore (https://crc-microbiome.stanford.edu).