Causal Relationship between the Gut Microbiota and Haematological Malignancies: A Two-Sample Mendelian Randomization Analysis

Abstract Background The gut microbiota has been implicated in the occurrence and development of haematological malignancies. However, the causal relationship between specific gut microbiota and haematological malignancies remains unclear. Methods In this study, we employed the Mendelian randomization (MR) approach to investigate the causal relationship between the gut microbiota and haematological malignancies. We selected the human gut microbiota as the exposure variable from the human whole-genome association analysis (GWAS) dataset of International Alliance MiBioGen. GWAS data of eight haematological malignancies from the FinnGen database were used as the outcome. We performed two-sample Mendelian randomization analysis using inverse-variance weighting (IVW), the weighted median estimator (WME), and MR‒Egger. Sensitivity analysis was also conducted to assess the stability of all MR results. Results Our findings revealed that 57 gut microbiota species may be causally related to haematological malignancies. Specifically, the family Oxalobacteraceae (OR = 1.828, 95% CI = 1.284 to 2.602, p = 0.0008) exhibited a strong positive correlation with the occurrence of ML. Additionally, the presence of the class Erysipelotrichia (OR = 8.738, 95% CI = 2.469 to 30.930, p = 0.001), the order Erysipelotrichales (OR = 8.738, 95% CI = 2.469 to 30.930, p = 0.001), and the family Erysipelotrichaceae (OR = 8.738, 95% CI = 2.469 to 30.930, p = 0.001) exhibited strong positive correlations with the occurrence of MCL. On the other hand, the class Methanobacteria (OR = 0.525, 95% CI = 0.338 to 0.816, p = 0.004), order Methanobacteriales (OR = 0.525, 95% CI = 0.338 to 0.816, p = 0.004), and family Methanobacteriaceae (OR = 0.525, 95% CI = 0.338 to 0.816, p = 0.004), as well as the class Actinobacteria(OR = 0.394, 95% CI: 0.209 to 0.746, p = 0.004), and genus Lachnospiraceae UCG001 (OR = 0.411, 95% CI = 0.232 to 0.728, p = 0.002), exhibited strong negative correlations with the occurrence of mature NK/T-cell lymphoma. These results suggest that the gut microbiota may play a significant role in the development of haematological malignancies. Conclusions Our findings suggest a causal relationship between the gut microbiota and haematological malignancies, which may contribute to providing new insights into the mechanisms of microbiota-mediated hematological malignancies. Additionally, these findings might lead to the identification of risk factors and early prediction of haematological malignancies.