Although there is evidence of an association between the fecal microbiota and colorectal cancer (CRC) risk in epidemiologic studies, there is a lack of data from large-scale population-based studies. To address this gap, we assessed the dysbiosis of the fecal microbiome in a large-scale study in Korea. We recruited 287 CRC patients from the Center for Colorectal Cancer, National Cancer Center Hospital, Korea to perform 16S rRNA gene sequencing of fecal samples. A total of 287 age- and sex-matched healthy participants were selected from 890 cohort of healthy Koreans that are publicly available (PRJEB33905). The microbial dysbiosis index (MDI) was calculated based on the differentially abundant species. The association between MDI and CRC risk was observed using conditional logistic regression. Alpha-diversity indices were not significantly different between CRC cases and controls. The first three principal coordinates derived by a principal coordinate analysis (PCoA) based on weighted UniFrac distance explained 41.24% of the overall microbial diversity, with a significant divergence of the microbial composition between CRC patients and controls (PERMANOVA p=0.001). Three enterotypes were found based on CRC patients’ microbial composition. Those who were in the third tertile of the MDI showed a significantly increased risk of CRC in the total population (OR: 6.59, 95% CI: 3.83-11.33, p-trend<0.001) compared to those in the lowest tertile. Similar results were found for men (OR: 6.58, 95% CI: 3.17-13.63, p-trend<0.001) and women (OR: 6.69, 95% CI: 2.91-15.37, p-trend<0.001). Dysbiosis in the fecal microbiota may be associated with an increased risk of CRC. Due to the potentially modifiable nature of the gut microbiota, our findings may have implications for CRC prevention among Koreans.

Key words: Fecal microbiome, 16S rRNA gene sequencing, Microbial dysbiosis, Colorectal cancer

Citation Format: Jeongseon Kim, Madhawa Gunathilake, Hyun Yang Yeo, Jae Hwan Oh, Byung Chang Kim, Nayoung Han, Bun Kim, Hyojin Pyun, Mi Young Lim, Young-Do Nam, Hee Jin Chang. Fecal microbial dysbiosis is associated with colorectal cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 755.