Left- and right-sided colorectal cancer (CRC) exhibit distinct molecular and clinicopathologic features. However, little is known about the spatial heterogeneity of microbial signatures. In this study the profiles and ecologic patterns of disease-associated intestinal microbiome were investigated in patients with an adenoma(s) or CRC at different anatomic locations.

A total of 690 stool, colonic aspirate, and mucosal biopsy samples were prospectively collected from 32 healthy, 30 adenoma, and 31 CRC patients.

CRC was associated with alterations in fecal and mucosal microbiomes. Furthermore, the overall composition of the mucosal microbiome, stratified by metacommunities, differed between the patients with left- and right-sided neoplastic lesions. Patients with right-sided CRC had an elevated inter-phylum ecologic network, while patients with left-sided CRC had an enriched abundance of Fusobacterium. Interestingly, rectal neoplasia harbored a tumor microbiome that was distinctly different from the tumor microbiome at other anatomic sites.

The mucosal microbiome of right-sided CRC was distinctly different from the mucosal microbiome of left-sided CRC patients, suggesting distinct microbial ecology and heterogeneous host-microbial ecologic relationships that may contribute to differences in the tumor microenvironment between left- and right-sided CRC.