Biom-01. Microbiota and Brain Cancer Metastasis

Brain metastases are the most common type of brain tumor, particularly in patients with lung, breast, and melanoma cancers. Despite surgical and radiotherapy advances, prognosis remains poor. Emerging targeted therapies, including those modulating the microbiome, offer potential improvements in treatment outcomes. This review explores the role of gut microbiota in brain metastasis via the gut-to-brain axis and examines the potential of microbiota-targeted therapies. A narrative review was conducted, analyzing recent studies on the gut microbiota’s influence on brain metastasis, focusing on animal and human models, immune modulation, and microbial signatures linked to metastasis progression. The microbiome plays a critical role in brain metastasis development across various cancer types, including non-small cell lung cancer, breast cancer, and melanoma. Distinct microbial signatures, including those from the oral microbiome, directly influence metastasis, while gut microbiota impact tumor initiation and progression. Notably, the absence of Alistipes, a bacterial genus, delays tumor onset in animal models, highlighting its role in brain metastasis initiation. In breast cancer models, gut microbiota depletion delayed metastasis onset, while kynurenic acid, a metabolite regulated by the gut microbiome, impaired cancer cell-vascular interactions, suggesting its involvement in tumor progression. In lung cancer, Intestinimonas and its metabolite spermine emerged as potential biomarkers and therapeutic targets, showing the gut-brain axis’s potential for treating brain metastasis. Additionally, microbiome depletion in mice enhanced anti-tumor immune responses, particularly through T cell modulation, emphasizing its immune-regulatory potential. These findings underscore the complex role of the microbiome in brain metastasis progression, suggesting microbiome-targeted therapies could offer promising avenues for treatment. Further studies are needed to explore the mechanistic roles of microbial dysbiosis and its interaction with immune responses to develop effective treatments for brain metastasis.