南方医科大学学报 ›› 2025, Vol. 45 ›› Issue (12): 2756-2766.doi: 10.12122/j.issn.1673-4254.2025.12.23

• • 上一篇    

肠道菌群、T细胞在结直肠癌发病中的因果关联:孟德尔随机化分析

喻珍妮1(), 高竟哲1, 孙惠1, 冯芹2, 那效旗1, 张宁1(), 沈昆双1, 王媛媛1, 王喜军1()   

  1. 1.黑龙江中医药大学药学院经方与现代中药融合创新全国重点实验室,黑龙江 哈尔滨 150040
    2.国家胶类中药工程技术研究中心,山东 聊城 252201
  • 收稿日期:2025-04-14 出版日期:2025-12-20 发布日期:2025-12-22
  • 通讯作者: 张宁,王喜军 E-mail:yzhennni@163.com;zhangning0454@163.com;xijunw@sina.com
  • 作者简介:喻珍妮,在读硕士研究生,E-mail: yzhennni@163.com
  • 基金资助:
    国家中医药多学科创新团队项目(ZYYCXTD-D-202407);东阿阿胶股份有限公司横向课题(22042240002);黑龙江省重点研发计划(2022ZX02C04)

Causal relationship between gut microbiota and T cell subsets in the development of colorectal cancer: a Mendelian randomization analysis

Zhenni YU1(), Jingzhe GAO1, Hui SUN1, Qin Feng2, Xiaoqi NA1, Ning ZHANG1(), Kungshuang SHEN1, Yuanyuan WANG1, Xijun WANG1()   

  1. 1.School of Pharmacy, State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Heilongjiang University of Chinese Medicine, Harbin 150040, China
    2.National Engineering Technology Research Center for Gelatin-based Traditional Chinese Medicine, Liaocheng 252201, China
  • Received:2025-04-14 Online:2025-12-20 Published:2025-12-22
  • Contact: Ning ZHANG, Xijun WANG E-mail:yzhennni@163.com;zhangning0454@163.com;xijunw@sina.com

摘要:

目的 采用孟德尔随机化(MR)方法探讨肠道菌群、T细胞功能与结直肠癌(CRC)风险之间的因果关系。 方法 从MiBioGen数据库收集肠道菌群,T细胞和结直肠癌数据从公开的GWAS数据中获得,对三者进行双样本MR分析。将逆方差加权法作为主分析方法,同时采用MR-Egger、加权中位数法(Weighted median)、简单模式法(Simple mode)、加权模式法(Weighted mode)作为补充,MR-PRESSO和MR-Egger回归方法来检测水平多效性,通过Cochran's Q检验来识别异质性,采用留一法进行敏感性分析。 结果 在肠道菌群与T细胞的正向MR分析中,有11种肠道菌群存在因果关系,其中有6种肠道菌与T细胞是正相关(Prevotella7属:P=0.003;Ruminococcaceae UCG011属:P=0.033;Ruminococcaceae UCG004属:P=0.010;Eubacterium brachy group属:P=0.005;Lachnospiraceae FCS020 group属:P=0.028;Coprobacter属:P=0.033),另外5种肠道菌呈负相关;在T细胞与结直肠癌的正向MR分析中,发现CD25++CD45RA-CD4非调节性T细胞与结直肠癌风险呈负相关(IVW: OR=0.935,95% CI:0.878~0.995,P=0.035);在肠道菌群与结直肠癌的正向MR分析中,有11种肠道菌群存在因果关系,其中有6种肠道菌与结直肠癌是正相关(Eubacterium xylanophilum group属:P=0.039;Selenomonadales目:P=0.014;Negativicutes纲:P=0.014;Bifidobacteriaceae科:P=0.048;Bifidobacteriales目:P=0.048;Coprococcus1属:P=0.033),另外5种肠道菌呈负相关。 结论 在肠道菌群、T细胞和结直肠癌三者关系中,Coprobacter属和Eubacterium xylanophilum group属是共有的菌,Eubacterium xylanophilum group属菌可通过促进CD25++ CD45RA- CD4非调节性T细胞的活性从而抑制结直肠癌的发展;而Coprobacter属菌可导致CD25++CD45RA-CD4非调节性T细胞失活从而使结直肠癌恶化。

关键词: 肠道菌群, T细胞, 结直肠癌, 孟德尔随机化, 因果关联

Abstract:

Objective To investigate the causal relationship between gut microbiota, T-cell function, and the risk of colorectal cancer. Methods Gut microbiota data from the MiBioGen database and T-cell and colorectal cancer data from publicly available GWAS datasets were obtained for analyzing the causality between gut microbiota, T-cell subsets, and the risk of colorectal cancer with two-sample Mendelian randomization (MR) analyses, using inverse variance weighting as the primary analytical method supplemented with MR-Egger, weighted median, simple mode, and weighted mode methods. Horizontal pleiotropy was assessed using MR-PRESSO and MR-Egger regression. Cochran's Q test was used to evaluate heterogeneity, and sensitivity analysis was performed using the leave-one-out method. Results In the Forward MR analysis of gut microbiota and T cells, 11 gut microbiota species showed causal relationships. Six of these species exhibited positive correlations with T cells, including Prevotella7 (P=0.003), Ruminococcaceae UCG011 (P=0.033), Ruminococcaceae UCG004 (0.010), Ebacterium brachy group (P=0.005), Lachnospiraceae FCS020 group (P=0.028), and Coprobacter (P=0.033), and the remaining 5 species showed negative correlations with T cells. Forward MR analysis of T cells and colorectal cancer suggested that CD25++CD45RA-CD4+ non-regulatory T cells were negatively correlated with colorectal cancer risk (IVW: OR=0.935, 95% CI: 0.878-0.995; P=0.035). The analysis of gut microbiota and colorectal cancer suggested that 11 gut microbiota species were causally associated with colorectal cancer, and 6 of them (Eubacterium xylanophilum group, P=0.039; Selenomonadales, P=0.014; Negativicutes, P=0.014; Bifidobacteriaceae, P=0.048; Bifidobacteriales, P=0.048; and Coprococcus1, P=0.033) showed positive correlations and the remaining 5 showed negative correlations. Conclusion Coprobacter spp. and Eubacterium xylanophilum group spp. are causally associated with both T cell activity and colorectal cancer risk, and the former bacteria induce inactivation of CD25++CD45RA-CD4+ non-regulatory T cells to promote colorectal cancer progression, whereas the latter bacteria promote CD25++CD45RA-CD4+ non-regulatory T cell activity to inhibit colorectal cancer development.

Key words: gut microbiota, T cells, colorectal cancer, Mendelian randomization, causal association