Kim Jeongseon, Gunathilake Madhawa, Yeo Hyun Yang, Oh Jae Hwan, Kim Byung Chang, Han Nayoung, Kim Bun, Pyun Hyojin, Lim Mi Young, Nam Young-Do, Chang Hee Jin
Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.
Department of Cancer Diagnostics, Research Institute, National Cancer Center, Goyang, Korea.
Cancer Res Treat. 2025 Jan;57(1):198-211. doi: 10.4143/crt.2024.382. Epub 2024 Jul 26.
The association between the fecal microbiota and colorectal cancer (CRC) risk has been suggested in epidemiologic studies. However, data from large-scale population-based studies are lacking.
In this case-control study, we recruited 283 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 283 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. Sparse Canonical Correlation Analysis was performed to integrate species data with microbial pathways obtained by PICRUSt2.
There is a significant divergence of the microbial composition between CRC patients and controls (permutational multivariate analysis of variance p=0.001). Those who were in third tertile of the MDI showed a significantly increased risk of CRC in the total population (odds ratio [OR], 6.93; 95% confidence interval [CI], 3.98 to 12.06; p-trend < 0.001) compared to those in the lowest tertile. Similar results were found for men (OR, 6.28; 95% CI, 3.04 to 12.98; p-trend < 0.001) and women (OR, 7.39; 95% CI, 3.10 to 17.63; p-trend < 0.001). Bacteroides coprocola and Bacteroides plebeius species and 12 metabolic pathways were interrelated in healthy controls that explain 91% covariation across samples.
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.
流行病学研究提示了粪便微生物群与结直肠癌(CRC)风险之间的关联。然而,缺乏来自大规模人群研究的数据。
在这项病例对照研究中,我们从韩国国立癌症中心医院结直肠癌中心招募了283例CRC患者,对粪便样本进行16S rRNA基因测序。从890例公开可用的韩国健康人群队列(PRJEB33905)中选取了283例年龄和性别匹配的健康参与者。基于差异丰富的物种计算微生物失调指数(MDI)。使用条件逻辑回归观察MDI与CRC风险之间的关联。进行稀疏典型相关分析,将物种数据与通过PICRUSt2获得的微生物途径整合。
CRC患者与对照组之间的微生物组成存在显著差异(置换多变量方差分析p = 0.001)。与最低三分位数的人群相比,MDI处于第三三分位数的人群在总体人群中患CRC的风险显著增加(优势比[OR],6.93;95%置信区间[CI],3.98至12.06;p趋势<0.001)。男性(OR,6.28;95%CI,3.04至12.98;p趋势<0.001)和女性(OR,7.39;95%CI,3.10至17.63;p趋势<0.001)也有类似结果。在健康对照组中,粪栖拟杆菌和普通拟杆菌物种以及12条代谢途径相互关联,解释了样本间91%的协变量。
粪便微生物群失调可能与CRC风险增加有关。由于肠道微生物群具有潜在的可改变性质,我们的发现可能对韩国人预防CRC有启示意义。