The emerging role of microbiota in neuro-oncology.

Primary and metastatic brain tumours are associated with poor clinical outcomes, largely owing to limited therapeutic advances and an incomplete understanding of brain tumour biology. Increasing evidence suggests that microbial communities play an important part in shaping systemic immunity and tumour biology. Microbes and microbial by-products from the gut and oral cavity can influence the central nervous system through the gut-oral-brain axis, providing potential mechanisms by which distant microbes shape the brain tumour microenvironment. A growing body of literature has identified distinct gut and oral microbial signatures associated with brain tumours and demonstrated that microbiota modulation can influence tumour growth and treatment response in preclinical models. In addition, emerging clinical data indicate that primary and metastatic brain tumours can harbour intracellular microbial elements. In this Review, we summarize current knowledge on the roles of the gut and oral microbiota and intratumoural microbial elements in brain tumour biology and treatment response. We present the technical challenges inherent to microbial studies in brain tumours due to low biomass and the high risk of contamination, and discuss key clinical, experimental and computational considerations needed for rigorous experimental design and standardized methodologies. Last, we discuss translational opportunities and future directions for moving the field towards clinical impact.