Background: The microbiome is an important biomarker associated with the pathogenesis and progression of disease in colorectal cancer (CRC). Genetic, dietary and environmental factors have been implicated in CRC microbial dysbiosis, however geographical distinctions in the microbiome of CRC are largely unknown. In this study, we characterize distinctions in the microbial diversity and microbial enrichment of CRC specimen obtained from a Nigerian and U.S. population. Methods: A validated microbiome bioinformatics pipeline that is generalizable across multiple next generation sequencing platforms was utilized. Microbial profiles for alpha diversity and enrichment were generated for two large, geographically distinct cohorts: (1) U.S. (n=498) and (2) Nigerian (n=65) cohorts. CRC specimen from Nigeria were compared to CRC specimen from the U.S. using the same microbial bioinformatics pipeline and methodology for analysis. Microbial differences stratified based on CRC microsatellite-instability (MSI) status were identified. Results: 9 unique microbial species were significantly enriched in the CRC specimen from the Nigerian cohort when compared to the US cohort. Subset analysis based on MSI status revealed enrichment of Faecalibacterium and Veillonella in the Nigerian cohort for both MSI and microsatellite stable (MSS) CRC (Table). Prevotella was significantly enriched in MSS CRC in the Nigerian cohort (OR=53.35, CI=10.34,275.37, p<0.001). There were no significant differences in alpha diversity between the Nigerian and U.S. cohorts (p>0.05). Conclusions: Several unique species with taxonomic diversity are enriched in Nigerian CRC and can be independently validated based on stratification by MSI status. Given the varied accessibility of diagnostic and therapeutic tools for CRC in these distinct geographical settings, understanding unique microbial biomarkers will provide the landscape to explore key microbial targets for therapy specific to this population.

*OR: Odds Ratio; CI: Confidence Interval. ^ΔMicrobes enriched in Nigerian colorectal cancer population when stratified for MSI and MSS status.