Gut dysbiosis and brain cancer: exploring the emerging role of sweeteners and food additives

Glioblastoma (GBM) remains the most aggressive primary brain malignancy, with a median survival of approximately 15 months, and its rising incidence has increased interest in modifiable dietary risk factors. Despite growing evidence that food additives disrupt gut microbial ecology and that gut dysbiosis influences neuro-oncological pathways, no previous review has systematically integrated these findings through the gut–brain axis. This narrative review synthesizes evidence from studies on food additives, gut microbiome, and glioblastoma to identify shared mechanistic pathways. Across five additive categories (artificial sweeteners, food colorants, preservatives, nanoparticles, and emulsifiers), a common dysbiotic signature emerged, characterized by depletion of short-chain fatty acid-producing bacteria, increased lipopolysaccharide (LPS) production, disruption of tryptophan metabolism, and impairment of intestinal and blood–brain barrier integrity. These changes converged on neuroinflammatory, immunosuppressive, and oncogenic pathways, including NF-κB, PI3K/AKT, and m 6 A-mediated epigenetic reprogramming. Among all additives reviewed, aspartame provided the most complete hypothesized mechanistic sequence linking gut dysbiosis, epithelial barrier dysfunction, and m 6 A-mediated upregulation of glioblastoma-associated genes, highlighting a plausible microbiome–epigenetic axis that warrants further investigation. These findings position food additives as biologically active modulators of the gut–brain axis with potential relevance to glioblastoma pathogenesis and provide a mechanistic framework to guide future microbiome-informed prevention, biomarker discovery, and therapeutic research.