This study investigates the clinical and microbial differences between left-sided colorectal cancer (LCC) and right-sided colorectal cancer (RCC), as well as the microbial profiles in tumor tissues (T) and peritumoral tissues (P) of colorectal cancer (CRC) patients. A total of 240 tissue samples were collected from CRC patients and classified based on the tumor location (LCC vs RCC) and tissue type (tumor vs peritumoral). Clinical data were recorded, and microbial analysis was performed using 16S rRNA sequencing. Bioinformatics analysis assessed microbial diversity and community composition, with statistical tests identifying significant differences between groups. LCC patients were older, heavier, and taller, with higher levels of tumor markers (CEA and CA199). Microbial analysis showed no significant differences in species evenness or richness between LCC and RCC; overall beta-diversity patterns did not differ significantly, although several taxa and predicted functions exhibited differential abundance between the two groups. Functional analysis revealed significant differences in KEGG Orthologs (KOs) and Clusters of Orthologous Groups (COGs) between LCC and RCC. Tumor tissue exhibited lower microbial diversity compared to peritumoral tissue, with significant differences in the microbial community structure. Our findings highlight the importance of considering sidedness and microbial composition in CRC management. The distinct microbial profiles in tumor and peritumoral tissues provide potential biomarkers for early detection and treatment response prediction. Future research should further explore these differences and their clinical implications.IMPORTANCEColorectal cancer (CRC) exhibits marked biological and prognostic differences between left-sided (LCC) and right-sided (RCC) tumors, yet the role of the tumor-associated microbiome stratified by sidedness remains poorly defined. In this study of 240 Chinese patients, we report the first integrated analysis combining clinical features with tissue microbial profiles (tumor vs peritumoral) according to the primary tumor location. We report differential abundance of specific taxa and predicted metabolic functions between LCC and RCC, plus significantly reduced diversity and altered structure in tumor tissue (T) compared with the adjacent normal tissue. These findings underscore the necessity of considering tumor sidedness and intratumoral microbiota in CRC classification, risk assessment, and precision therapy and highlight candidate microbial signatures as potential noninvasive biomarkers for early detection, sidedness prediction, and personalized treatment strategies.
Li et al. (Fri,) studied this question.