Causal Associations of Gut Microbiota Species With Lymphoma: A Two-Sample Mendelian Randomization Study

This study aims to focus on GM at species level, exploring the causal associations with different kinds of lymphoma to provide some information on potential intervention directions in lymphoma. Data of GM taxa were extracted from the genome-wide association study conducted by the MiBioGen and Dutch Microbiome Project (DMP), and those of lymphomas were obtained from the FinnGen consortium. Inverse variance weighted (IVW) method and Bonferroni multiple correction were utilized to assess the causal associations of GM species with different kinds of lymphoma. The effect size was expressed by odds ratios (ORs) with 95% confidence intervals (CIs). Reverse causal association analysis has also been performed. Additionally, scatter plots and leave-one-out test were conducted for sensitivity analysis. After correction, the IVW estimates suggested that elevated relative abundance of species Faecalibacterium_prausnitzii had a negatively causal association with increased odds of Hodgkin's lymphoma (HL) (OR = 0.584, 95% CI: 0.516-0.662). Relative abundance of species Gordonibacter_pamelaeae, Holdemania_filiformis, Sutterella_wadsworthensis and Coprococcus_sp_ART55_1 was negatively associated with follicular lymphoma (FL) odds, whereas that of species Bifidobacterium_catenulatum and Coprococcus_comes were positively associated with FL odds (all p < 0.05). Relative abundance of species Akkermansia_muciniphila and Coprococcus_sp_ART55_1 had a negatively causal association with non-follicular lymphoma (NFL) odds, respectively, while that of Bacteroides_uniformis had a positive one (all p < 0.05). Relative abundance of species Flavonifractor_plautii was negatively linked to diffuse large B-cell lymphoma (DLBCL) risk (OR = 0.471, 95% CI: 0.344-0.645). Relative abundance of species Eggerthella_unclassified was positively associated with T/NK cell lymphoma (TNK) risk while that of Ruminococcus_lactaris was negatively associated with TNK risk (all p < 0.05). Elevated relative abundance of Parabacteroides_unclassified was associated with higher risk of non-Hodgkin's lymphoma (NHL) (OR = 1.955, 95% CI: 1.654-2.312). The relative abundance of species Holdemania_filiformis was negatively associated with mantle cell lymphoma (MCL) risk (OR = 0.637, 95% CI: 0.544-0.746). The relative abundance of species Rothia_mucilaginosa and Lachnospiraceae_bacterium_3_1_46FAA had positively causal association with marginal zone lymphoma (MZL) risk, while that of species Alistipes_senegalensis had a negative one (all p < 0.05). This study identified 16 GM species that have potential causal associations with different kinds of lymphoma, which provided some new idea for further exploration on prevention and treatment targets in lymphoma.