Relationship between gut microbiota and breast cancer: a Mendelian randomization analysis of mediating effects based on inflammatory proteins

Abstract Background: Breast cancer is associated with dysbiosis of dysbiosis of gut flora. However, the mechanisms of how gut microbiota mediate breast cancer disease are not clear, and exploring possible mediating mechanisms is key to investigating the study of the mechanisms that gut microbiota contribute to breast cancer development. Methods: A two-sample two-way Mendelian randomization (MR) analysis was employed, with publicly available genome-wide association study (GWAS) data, to investigate role of abnormal gut microbiota in breast cancer development. It focuses on assessing the potential mediation by circulating inflammatory proteins. The primary methodology employed for identifying gut microbiota (GM) associated with breast cancer and examining the impact of inflammatory markers is the variance inverse weighting method, supplemented by the MR-Egger method and weighted median method. This research aims to offer novel insights into potential therapeutic interventions for breast cancer. Result: Seven genera and three inflammatory proteins were determined to be associated with breast cancer. The inflammatory protein Fibroblast growth factor 21 levels mediated the effect of the intestinal bacterium Adlercreutzia on the course of breast cancer in 11.1% of cases, and the inflammatory protein CD40L receptor levels mediated the effect on the gut microbiotaParabacteroides on the course of breast cancer in 9% of cases.