The causal relationship of gut microbiota in progression of seven common hematological malignancies

Abstract

Purpose: Evidence from observational researches and clinical trials showed the relationship between gut microbiomes (GMs) and hematological malignancies. Nevertheless, the causal role of GM taxa in development of hematological malignancies remains to be explored. Therefore, we aim to assess the causal links between 196 GM taxa and seven common hematological malignancies using the two-sample Mendelian randomization (MR) analyses. Methods: All datasets were derived from published genome-wide association studies (GWAS) statistics. The primary analysis was performed using random effects inverse variance weighted (IVW). To verify the robustness of the MR results, we performed several sensitivity analyses such as Egger intercept test, the Cochran Q test, MR pleiotropy residual sum and outlier (MR-PRESSO), and leave-one-out analysis. Results: We revealed the family Oxalobacteraceae would increase the risk of myeloid leukemia by the Bonferroni correction [odds ratio (OR): 2.08, 95% CI: 1.49, 2.90, p = 1.68E-05]. In addition, 22 nominally significant associations between genetic liability in GMs and hematological malignancies were also found (P < 0.05). Sensitivity analysis verified the robustness of the above causal relationships. Conclusion: This study confirms the causal relationship between GMs and hematological malignancies and may provide new insights to the mechanistic and clinical researches of GM-mediated hematological malignancies.