Exploration of the GM-IC-DLBCL Axis: A Mendelian Randomization Analysis of the Gut Microbiota, Immune Cells, and Diffuse Large B-Cell Lymphoma.

Aims/Background This study aims to investigate the causal relationship among gut microbiome (GM), immune cells (IC), and diffuse large B-cell lymphoma (DLBCL) using the Mendelian randomization (MR) approach. Methods This analysis included GM data (471 taxa; n = 5959), genome-wide association study (GWAS) data on 731 IC phenotypes, and DLBCL data (1373 cases and 345,118 controls) from the FinnGen Consortium. A two-sample bidirectional MR analysis established causal links between GM, IC phenotypes, and DLBCL, followed by a two-step mediation analysis to assess immune cell mediation. Results Potential causal links were observed among 15 GM taxa, 38 IC phenotypes, and DLBCL. Mediation analysis revealed 14 possible gut microbiota-immune cell-diffuse large B-cell lymphoma (GM-IC-DLBCL) axes, with quantifiable effects in five. The maximum and minimum mediating effects included g__Roseibacillus (odds ratio [OR] = 3.30, 95% confidence interval [CI]: 1.22-8.91, p < 0.05; 10.4% via "CD45RA on naive CD8br cells") and s__Lachnospira rogosae (OR = 1.14, 95% CI: 1.01-1.28, p < 0.05; 5.8% via "CD127 on CD28- CD8br cells"), respectively. Conclusion This study suggests that GM may contribute to DLBCL pathogenesis through IC mechanisms, supporting the potential existence of a GM-IC-DLBCL axis.