The Role of 473 Intestinal Microbiota and 91 Inflammatory Factors in Breast Cancer Risk: Insights From Mendel Randomization and its Implications for Diagnosis and Treatment.

Abstract

Background: The association between gut microbiota, inflammatory factors, and breast cancer risk has attracted significant attention in recent years. However, the causal relationships remain unclear.

Methods: A bidirectional 2-sample Mendelian Randomization (MR) analysis was conducted to explore the causal relationships among 473 gut microbiota taxa, 91 inflammatory factors, and breast cancer. Mediation analysis was performed to assess the potential role of inflammatory factors in mediating the link between gut microbiota and breast cancer risk. At the same time, we used external datasets for validation.

Results: MR analysis revealed that gut microbiota taxa, such as Bacteroides eggerthii and Faecalicatena lactaris, were negatively associated with breast cancer risk, suggesting a protective effect. In contrast, other taxa, including Bacteroides stercoris and Bifidobacteriaceae, were positively associated with breast cancer risk. Several inflammatory factors, such as Caspase 8, CXCL10, FLT3L, IL-33, and LIFR, demonstrated negative associations with breast cancer risk, indicating potential protective roles. Mediation analysis identified FLT3L as a partial mediator in the relationship between Faecalicatena lactaris and breast cancer risk, as well as in the association between Mycoplasmoidaceae and breast cancer.

Conclusions: This study uncovers potential causal relationships between gut microbiota, inflammatory factors, and breast cancer development, offering new insights into biological targets and intervention strategies for breast cancer prevention and treatment.