Gut Microbiota and Immune System Interplay Influences Breast Cancer Risk

Breast cancer remains one of the most prevalent cancers worldwide and a significant cause of cancer-related mortality among women. Despite advancements in screening methods and treatment options, managing advanced stages of the disease poses ongoing challenges. Consequently, researchers are exploring new avenues to better understand risk factors and develop preventative strategies.

A recent study published in Biomolecules and Biomedicine by Zhang and colleagues highlights the potential role of the gut microbiota—the trillions of microorganisms residing in the human digestive system—in modulating breast cancer risk. Using large-scale genetic analyses, the researchers identified specific microbial traits and immune cell populations that could influence the likelihood of developing breast cancer.

The gut microbiome plays a crucial role in regulating metabolism and immune responses. Disruptions in its balance, known as dysbiosis, have been associated with various diseases, including cancers. The study employed Mendelian Randomization, a method that uses genetic variants to infer causal relationships, minimizing confounding factors common in observational studies. Through this approach, 15 microbial traits were found to be significantly associated with breast cancer risk. Pathways involved in menaquinol-8 (a form of vitamin K2) and amino acid biosynthesis correlated with increased risk, while pathways like fatty acid oxidation and biotin (vitamin B7) biosynthesis appeared protective.

Certain bacterial species also showed noteworthy associations; for instance, Pseudoflavonifractor and Parabacteroides merdae were linked to higher breast cancer risk, whereas Roseburia and Bacteroides intestinalis seemed to offer protective effects.

Further analysis distinguished between breast cancer subtypes, specifically HER2-positive and HER2-negative forms. While microbial associations varied between subtypes, the pathway related to biotin biosynthesis consistently indicated a reduced risk, suggesting some microbiome functions may offer broad protective effects.

The study also delved into how immune pathways mediate the relationship between gut microbes and cancer risk. It found that certain microbial effects are partly channeled through immune cell populations, such as CD4+CD8+ double-positive T cells, which have been observed in patients with advanced breast cancer. Although these immune-mediated effects were modest, they provide valuable insight into how gut microbes influence cancer development via immune modulation.

Implications for prevention and treatment are substantial. Interventions like dietary modifications or probiotics could potentially shift the microbiome toward protective profiles. Additionally, understanding immune pathways affected by microbes opens avenues for new therapies, and microbial or immune signatures could enhance risk prediction and personalizing preventive strategies.

The findings are currently limited to individuals of European ancestry and specific breast cancer subtypes; future research must include more diverse populations and broader cancer types. The authors underscore that this research supports the existence of a gut–immune–cancer axis in breast cancer, paving the way for microbiome-informed approaches in cancer prevention and treatment.

Source: https://medicalxpress.com/news/2025-09-gut-microbiota-immune-response-linked.html