Multi-omics association investigation of the relationship between gut microbiota and the development of colorectal cancer

BACKGROUND: The human gut mucosal microbiota is crucially involved in colorectal cancer (CRC) development. However, a comprehensive analysis of host-microbiota interactions remains limited. METHODS: Intestinal mucosal samples were collected from patients admitted to the Affiliated Suzhou Hospital of Nanjing Medical University from September 2020 to May 2021. Participants were diagnosed with colorectal cancer (n = 30), tubular adenoma with high-grade intraepithelial neoplasia (n = 25), or tubular adenoma with low-grade intraepithelial neoplasia (n = 25), or hyperplastic polyp (n = 30). Using microbiomics and metabolomics analyses, we investigated associations among intestinal mucosal microorganisms, bile acids, and short-chain fatty acids during CRC development. RESULTS: Our findings revealed gut microbial richness and diversity, as well as the relative abundances of beneficial bacteria (e.g., Lachnospiraceae, Faecalibacterium, and Blautia), decreased with increasing malignancy of mucosal lesions. During the progression from benign hyperplasia to neoplastic lesions, changes in glycocholic acid, taurocholic acid, glycoursodeoxycholic acid, and taurodeoxycholic acid, acetate, butyrate, isobutyrate, and isovalerate are correlated with alterations in the intestinal mucosal microbiota. Random forest modeling and ROC analysis in this preliminary, single-center study suggested that intestinal mucosal microorganisms and bile acids hold promise as potential combined biomarkers for CRC diagnosis. However, further validation in larger, multi-center cohorts is required to confirm their robustness and clinical utility. CONCLUSIONS: Our study initially suggests a potential association between intestinal mucosal bacteria and bile acids as well as short-chain fatty acids in the progression from benign hyperplasia to neoplastic lesions in the colon, providing new clues for understanding the role of gut microbiota in the process of colorectal cancer development.