Emerging Insights into the Role of the Microbiome in Brain Gliomas: A Systematic Review of Recent Evidence.

Abstract

Gliomas, particularly glioblastoma multiforme, remain among the most lethal brain tumours despite multimodal therapy. Increasing evidence indicates that systemic factors, including the gut microbiota, may influence glioma progression through immune, metabolic, and neurochemical pathways. We conducted a comprehensive systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines to synthesize recent evidence on the role of gut and intratumoral microbiota in glioma biology. Peer-reviewed studies published within the last five years were identified through structured searches of major biomedical databases, and original studies using human cohorts, animal models, or Mendelian randomization approaches were included. The 17 studies met the eligibility criteria. Glioma was consistently associated with gut dysbiosis characterized by a reduced <i>Firmicutes</i>:<i>Bacteroidetes</i> ratio and enrichment of <i>Verrucomicrobia</i>, particularly <i>Akkermansia</i>, alongside decreased short-chain fatty acids and altered neurotransmitter profiles, contributing to neuroinflammation, immune suppression, and blood-brain barrier dysfunction. Antigenic mimicry by Bacteroidetes-derived peptides may impair antitumour T-cell responses, while intratumoral <i>Fusobacteriota</i> and <i>Proteobacteria</i> appear to promote angiogenesis and pro-inflammatory chemokine expression. In contrast, SCFA-producing taxa such as <i>Ruminococcaceae</i> and probiotic genera including <i>Lactobacillus</i> and <i>Bifidobacterium</i> show protective associations. Evidence is limited by small cohorts and methodological heterogeneity. Standardized humanized models and integrated multi-omics approaches are required to clarify causal mechanisms and support microbiome-targeted therapies in glioma.