Gut microbiota and glioblastoma: composition, mechanisms, and therapeutic interventions

BACKGROUND: Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor, associated with an exceedingly poor prognosis. The gut microbiota, a complex community of microorganisms, critically regulates host physiological homeostasis and communicates bidirectionally with the central nervous system via the gut-brain axis. Emerging evidence suggests that dysbiosis within this axis may profoundly influence GBM pathophysiology through inflammatory and immune-modulatory mechanisms, but a comprehensive synthesis of this complex interplay and its clinical implications remains vital for therapeutic advancement. MAIN BODY: This narrative review systematically synthesizes the existing literature from MEDLINE (via PubMed), Scopus, and Web of Science, covering publications up to September 26, 2025, to elucidate the multifaceted role of the gut microbiota-brain axis in GBM. Our study focuses on three critical domains: microbial composition alterations, mechanistic insights, and therapeutic interventions. The review confirms significant alterations in the gut microbial community in GBM across both clinical and preclinical models, with consistent enrichment or depletion of specific bacterial taxa that may affect tumor pathogenesis and prognosis. Mechanistically, gut microbiota-derived metabolites and receptor interactions are shown to modulate GBM progression by influencing tumor-promoting hallmarks, including metabolic reprogramming, immune evasion, and sustained proliferative signaling. Furthermore, the efficacy of standard treatments, including temozolomide chemotherapy and immune checkpoint inhibitors, is actively modulated by the patient's gut microbiota composition. Dietary approaches and traditional medicines further demonstrate microbiota-dependent effects on tumor progression and immune regulation. CONCLUSION: This review underscores the critical and intricate role of the gut microbiota-brain axis in GBM biology, affecting both tumor progression and therapeutic responsiveness. The compiled evidence establishes a clear rationale for advancing microbiota-targeted strategies as novel adjunctive interventions to enhance clinical outcomes for individuals with GBM. CLINICAL TRIAL NUMBER: Not applicable.