Causal relationship between gut microbiota and T cell subsets in the development of colorectal cancer:a Mendelian randomization analysis
YU Zhenni
GAO Jingzhe
SUN Hui
Feng Qin
NA Xiaoqi
ZHANG Ning
SHEN Kungshuang
WANG Yuanyuan
WANG Xijun
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.
Keywords：gut microbiotaT cellscolorectal cancerMendelian randomizationcausal association
Publication Date：2025-12-20
Online Publishing Date：2025-12-31(First online date of this platform, not the publication date of the document)
Pages：11( 2756-2766 )