AUTHOR=Xiao Jinyin , Guo Xiajun , Lin Youwei , Wang Zhenquan 

TITLE=The causal relationship between immune cell-mediated gut microbiota and ulcerative colitis: a bidirectional two-sample, mediation Mendelian randomization analysis

JOURNAL=Frontiers in Nutrition

VOLUME=11

YEAR=2024

URL=https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2024.1433545

DOI=10.3389/fnut.2024.1433545

ISSN=2296-861X

ABSTRACT=<sec id="sec1"><title>Background</title><p>Numerous studies have highlighted the close association between gut microbiota and the development of ulcerative colitis (UC), yet research on whether immune cells mediate this process remains scarce. This study utilizes various Mendelian randomization (MR) methods to investigate the causal relationship between gut microbiota and UC, further exploring the mediating role of immune cells in this process.</p></sec><sec id="sec2"><title>Methods</title><p>Genome-wide association study (GWAS) summary statistics for 473 gut microbiota, 731 immune cell phenotypes, and UC were obtained from the GWAS catalog database. Single nucleotide polymorphisms (SNP) were used as instrumental variables (IV) to validate the causal relationship between gut microbiota and UC through two-sample MR and Bayesian weighted MR (BWMR), and reverse MR was employed to explore the presence of reverse causal effects. Two-step MR was applied to identify immune cell mediators and evaluate their mediation effects.</p></sec><sec id="sec3"><title>Results</title><p>The study revealed a causal relationship between 20 gut microbiota and UC, with 14 microbiota acting as protective factors for UC and 6 as risk factors. Mediation MR identified 26 immune cell mediators, among which the association between CD11b on Mo MDSC and <italic>Bifidobacterium bifidum</italic> (<italic>B. bifidum</italic>) was most significant (<italic>p</italic> = 0.0017, OR = 1.4540, 95% CI: 1.1504–1.8378). Mediation MR analysis indicated that the mediation effect of CD11b on Mo MDSC between <italic>B. bifidum</italic> and UC was −0.0385, with a mediation effect ratio of 16.67%.</p></sec><sec id="sec4"><title>Conclusion</title><p>There is a clear causal relationship between certain gut microbiota and UC, and CD11b on Mo MDSC is a significant mediator between <italic>B. bifidum</italic> and UC, providing new insights for the clinical treatment of UC.</p></sec>