Microbiota recruitment for brain cancer management

The interplay between the gut microbiota and the central nervous system is increasingly recognized as a critical factor in the pathogenesis and treatment responsiveness of brain tumors. The brain interacts with microbial communities, both systemically through the gut-brain axis and locally within the tumor microenvironment. The gut microbiota regulates systemic immunity and modulates key processes such as blood-brain barrier integrity, cytokine signaling, and neuroinflammation—all of which influence glioma development and resistance to therapies. Evidence from preclinical models indicates that modulation of the gut microbiota can enhance anti-tumor immunity and improve responses to immune checkpoint inhibitors (ICIs). In parallel, recent discoveries reveal the presence of bacterial DNA and viable microbes within glioma tissue initiating signaling cascades that modulate immune cell recruitment and polarization. These microbial-immune interactions shape the tumor’s immune landscape, favoring either anti-tumor immunity or immune evasion depending on the context. Additionally, microbial-derived metabolites, such as short-chain fatty acids, have been shown to influence gene expression through epigenetic mechanisms, including histone acetylation and regulation by non-coding RNAs. Such effects may contribute to tumor cell plasticity, metabolic reprogramming, and resistance to therapy. The reciprocal influence of glioma and its treatment on gut microbial ecology is also an important consideration. Therapeutic interventions such as antibiotics, corticosteroids, and chemotherapy can significantly disrupt the gut microbiota, potentially diminishing the efficacy of microbiota-driven immunomodulation. Therefore, understanding the bidirectional dynamics of the gut-brain-tumor axis is essential for the development of microbiome-informed therapies. Despite these promising insights, several challenges remain. In this review, we synthesize current knowledge on the role of the gut and intratumoral microbiota in glioma biology and treatment, focusing on immune modulation, therapeutic responsiveness, and potential for microbiota-informed interventions. We also discuss existing controversies, methodological limitations, and future research priorities in the context of advancing microbiome-based strategies in neuro-oncology.