Exploring the role of succinyl carnitine in the association between CD39⁺ CD4⁺ T cell and ulcerative colitis: A Mendelian randomization study.

Objective: This study aimed to investigate the potential causal relationship between immune cell and the risk of ulcerative colitis (UC), and to explore whether serum metabolites may mediate this association, thereby suggesting potential biomarkers or therapeutic targets. Methods: We conducted a Mendelian randomization (MR) analysis using summary statistics from genome-wide association studies to evaluate both the direct effects and potential mediating roles of 731 immune cells and 1,400 serum metabolites in relation to UC. Instrumental variables were rigorously selected based on genome-wide significance and linkage disequilibrium thresholds. The primary analytical method was inverse variance weighted, supplemented by MR-Egger regression and weighted median methods to ensure robustness. Cochran's Results: We identified a statistically significant positive causal effect of CD39⁺ CD4⁺ T cell on UC risk (OR = 1.05, 95% CI = 1.03-1.08, Conclusion: Our findings suggest that CD39⁺ CD4⁺ T cell may increase the risk of UC, potentially by modulating the levels of succinyl carnitine (C4DC). These results indicate a potential immunometabolic pathway in UC pathogenesis and highlight CD39⁺ CD4⁺ T cell and C4DC as promising targets for further research. However, additional experimental validation is required to confirm these findings and assess their clinical relevance.