Causal relationship between gut microbiota and malignant lymphoma:a two-way two-sample Mendelian randomization study

Abstract Background The significance of gut microbiota in human health is gaining attention, leading to a rise in observational and clinical studies focused on understanding the factors and mechanisms that influence gut microbiota in various malignancies, such as lymphoma.However, the precise causative link between the gut microbiota and malignant lymphoma remains uncertain.In recent times, the employment of Mendelian randomization(MR) analysis in investigating the gut microbiota has demonstrated substantial scientific merit in uncovering the association between the intestinal microbiota and various diseases. Moreover, the utilization of MR analysis holds promise in elucidating the causative link that exists between the gut microbiota and lymphoma. Materials and methods Bidirectional two-sample MR analysis was used to examine the causal relationship between malignant lymphoma and gut microbiota. The summary of gut microbiota statistics used in this study came from a large-scale genome-wide MiBioGen consortium project involving 18,340 subjects from a multi-ethnic group. Summary statistics for malignant lymphoma were obtained from the OPEN GWAS website with the participation of 490,803 European subjects. According to the inclusion standard screening single nucleotide polymorphism (SNP) as a tool variable (IV), the potential causative link between gut microbiota and malignant lymphoma was examined by inverse variance weighting method, MR-Egger method, weighted median method, weighted model method and simple mode method. Then, reverse MR analysis was performed on bacteria found to be causally related to malignant lymphoma in forward MR analysis. Results In this study, seven causal relationships between intestinal microbiota and malignant lymphoma were determined by five MR analyses, phylon Bacteroidetes (odds ratio (OR) = 1.31,95% CI = 1.02–1.68,P = 0.032),class Bacilli(OR = 1.22 ,95% CI = 1.00-1.49,P = 0.048),family Rikenellaceae(OR = 1.27 ,95% CI = 1.04–1.55,P = 0.022),genus Eubacterium nodatum group(OR = 1.13 ,95% CI = 1.00-1.27,P = 0.046),genus Oxalobacter(OR = 1.23 ,95% CI = 1.06–1.43,P = 0.006),genus Parabacteroides(OR = 1.41 ,95% CI = 1.41–1.99,P = 0.049), there was a causal relationship between the genus Sellimonas(OR = 1.18 ,95% CI = 1.03–1.35,P = 0.016) and malignant lymphoma, and no significant level pleiotropy and heterogeneity were found in the instrumental variables. It should be noted that there is no reverse causality between malignant lymphoma and gut microbiota. Conclusion This investigation delved into a plausible causal connection between the gut microbiota and malignant lymphoma. It presents a novel concept and theoretical foundation for future research on the intestinal flora's relationship to lymphoma.