The landscape of tissue-resident microbiota across normal, polyp, and colorectal cancer tissues.

Emerging evidence suggests that tissue-resident microbiota (TRM) is associated with tumor biology; however, their distribution and compositional characteristics across different colorectal tissue types remain incompletely defined. Here, we conducted a comprehensive cross-sectional analysis of TRM distribution and abundance across 1134 clinical specimens, including normal mucosa, precancerous polyps, and colorectal cancer (CRC) tissues. Our results reveal distinct microbial profiles among these diagnostic groups, with consistent differences in community composition between normal, polyps, and CRC samples. Integrative analyses further identified microbial signatures capable of distinguishing tissue categories and reflected differences in the local tumor microenvironment. In contrast, intratumoral microbiota composition showed subtle variation across established tumor stages and was not associated with clinical outcomes. These findings define diagnostic group-associated patterns of TRM in colorectal tissues and establish a foundation for future mechanistic investigations into the biological roles of TRM in colorectal cancer.