Microbial Community Heterogeneity Within Colorectal Neoplasia and its Correlation With Colorectal Carcinogenesis.

BACKGROUND & AIMS Gut microbial dysbiosis has pivotal involvement in colorectal cancer (CRC). However, the intratumoral microbiota and its association with CRC progression remain elusive. We aimed to determine the microbial community architecture within a neoplasia (CRC or adenoma) and its contribution to colorectal carcinogenesis. METHODS We collected 436 tissue biopsies from patients with CRC (n = 36) or adenoma (n = 32) (2-6 biopsies from a neoplasia plus 2-5 biopsies from adjacent normal tissues per individual). Microbial profiling was performed using 16S ribosomal RNA gene sequencing with subsequent investigation of microbiota diversities and heterogeneity. The correlation between microbial dysbiosis and host genetic alterations (KRAS mutation and microsatellite instability) in all neoplasia biopsies was also analyzed. RESULTS We discovered that intra-neoplasia microbial communities are heterogeneous. Abundances of some CRC-associated pathobionts (eg, Fusobacterium, Bacteroides, Parvimonas, and Prevotella) were found to be highly varied within a single neoplasia. Correlation of such heterogeneity with CRC development revealed alterations in microbial communities involving microbes with high intra-neoplasia variation in abundance. Moreover, we found that the intra-neoplasia variation in abundance of individual microbes changed along the adenoma-carcinoma sequence. We further determined that there was a significant difference in intra-neoplasia microbiota between biopsies with and without KRAS mutation (P < .001) or microsatellite instability (P < .001), and illustrated the association of intratumoral microbial heterogeneity with genetic alteration. CONCLUSIONS We demonstrated that intra-neoplasia microbiota is heterogeneous and correlated with colorectal carcinogenesis. Our findings provide new insights on the contribution of gut microbiota heterogeneity to CRC progression.