Causal pathways in Lymphoma: The role of serum metabolites and immune cells determined by Mendelian randomization

•Establishing Causality: This study employed various two-sample Mendelian randomization (TSMR) techniques, including Inverse Variance Weighted (IVW), Weighted Median, MR-Egger, Simple Mode, and Weighted Mode, to effectively confirm the direct causal links between 1400 types of serum metabolites, 731 types of immune cells, and six different types of lymphoma. This finding provides a new genetic perspective on the pathophysiological mechanisms of lymphoma.•Innovative Analytical Techniques: Not only did this study apply standard Mendelian randomization methods, it also included reverse MR analysis and two-step MR mediation techniques. The former was used to explore reverse causality, while the latter quantified the proportion of lymphoma effects mediated by serum metabolites through immune cells. The application of these methods enhanced the rigor of the research design and the interpretative power of the results.•Mediation Analysis: Through two-step MR mediation analysis, this study identified the mediating role of serum metabolites in the development of lymphoma and the function of immune cells. These results reveal potential metabolic pathways that regulate the interaction between immune cell function and lymphoma progression, offering potential intervention points for targeted therapy.•Reliability and Sensitivity: Through MR-Egger regression and leave-one-out sensitivity tests, this study verified the stability and reliability of the results. These tests showed that the analysis was not affected by outliers among the instrumental variables and that there was no significant genetic heterogeneity, thus enhancing the credibility of the study’s conclusions.•Clinical Significance and Future Research: The study’s findings highlight the importance of using immune cells as biomarkers in lymphoma patients. Future research should further explore other potential biomarkers and therapeutic targets, as well as how to optimize treatment strategies through the interaction of immune cells and metabolic pathways. This will help improve the early diagnosis and treatment of lymphoma, while deepening our understanding of targeted immunotherapy and metabolic strategies in the management of lymphoma. Prior research has demonstrated significant roles of metabolites and immune cells in the progression of lymphoma. Mendelian randomization studies have been conducted to assess the causal relationships among serum metabolites, immune cells, and lymphoma, further exploring the media