Causal associations between human gut microbiota and Multiple Myeloma: a mendelian randomization study

Abstract

Background: Numerous clinical studies have indicated a close connection between the human gut microbiome and multiple myeloma, yet the presence of a causal genetic link between them remains unclear. This study employs a two-sample Mendelian Randomization (MR) approach to assess the potential causal relationship between these two factors. Methods:We used genome-wide association study (GWAS) statistics for the human gut microbiome obtained from the MiBioGen database, and multiple myeloma data from the UK Biobank (UKB). The primary analysis was conducted using the inverse variance weighted (IVW) method for two-sample MR to assess the causal relationship between the gut microbiome and multiple myeloma. Sensitivity analyses were performed to ensure the robustness of the results. Results:Our findings, predominantly based on the IVW method, support a causal relationship between six gut microbial taxa and multiple myeloma. We observed positive associations with increased risk of multiple myeloma for Anaerotruncus from the human colon (p=0.033) and the Bilophila genus (p=0.033), suggesting these microbiota may elevate the risk of the disease. Conversely, negative correlations potentially related to reduced risk were found for the Slackia genus (p=0.022), Victivallis genus (p=0.046), Butyrivibrio genus (p=0.044), and Ruminiclostridium5 genus (p=0.032). No reverse causality was detected between multiple myeloma and the six specific gut microbial taxa. Conclusion:Our team pioneered a Mendelian Randomization study on the causal relationship between specific gut microbiota and multiple myeloma, providing meaningful insights into the potential mechanisms from a genetic perspective. This research offers valuable references for the early prevention of multiple myeloma and the improvement of disease progression.