This study aims to explore the causal association between the mediation of intestinal micrococci and the occurrence of breast cancer through CD45RA⁺ immune cells.

Mediating mendelian randomization (MR) analysis was used to establish the association between intestinal micrococci, CD45RA⁺ immune cells and breast cancer. The data of the gut microbiome were derived from the genome-wide association studies (GWAS) database, which included the metagenomic sequencing data of the gut microbiome of multiple populations. The breast cancer data originated from large-scale GWAS studies of the European female population. By filtering and selecting these data, we obtained the data associated with the occurrence of intestinal micrococci and breast cancer, and used MR analysis to remove weak instrumental variables. The role of CD45RA⁺ immune cells in the occurrence of breast cancer was explored by methods such as total effect analysis, reverse MR analysis, MR analysis of CD45RA⁺ immune cells in the Enterococcus family, MR analysis of CD45RA⁺ immune cells in breast cancer, mediating effect calculation, and sensitivity analysis.

The abundance of intestinal micrococci is positively correlated with the expression of CD45RA⁺ immune cells significantly (IVW OR = 1.385, 95% CI:1.017-1.684, P = 0.034). The expression of CD45RA⁺ immune cells was negatively correlated with the incidence of breast cancer (IVW OR = 0.769, 95% CI: 0.545-0.995, P = 0.017). The abundance of intestinal micrococci was significantly negatively correlated with the total effect on the incidence of breast cancer (IVW OR = 0.857, 95% CI: 0.745-0.955, P = 0.016) .

This study confirmed that the intestinal micrococcus family mediates the reduction of the risk of breast cancer incidence through CD45RA⁺ immune cells, providing a basis for the intervention strategy targeting the microbiota-immune axis.