Interplay Between the Ketogenic Diet and the Gut Microbiome in Glioblastoma: A Comprehensive Review of Mechanisms and Clinical Implications Publisher Pubmed



Mirzai M ; Eslami M ; Azizi A H ; Lotfi P ; Alavi Khoshhall S A ; Mirzaei A ; Habibi M A
Source: Nutrition and Cancer Published:2026

Abstract

Glioblastoma (GBM) is an aggressive glioma associated with poor prognosis and a median survival of under one year. Standard therapies—surgery, radiotherapy, and temozolomide—impose substantial financial burdens and reduce quality of life, driving interest in less invasive adjunctive approaches. The ketogenic diet (KD) has shown promise by targeting tumor metabolic vulnerabilities, as GBM cells rely heavily on glucose and exhibit limited capacity for ketone metabolism. Although KD is well-validated in epilepsy and diabetic ketoacidosis, its application in GBM yields inconsistent results due to small trials, low adherence, and variability in study designs. Emerging evidence suggests that interindividual differences in gut microbiota (GM) composition may significantly contribute to this inconsistency. GM modulates host metabolism, influences KD efficacy, and exhibits bidirectional interactions with tumor progression. Notably, glioma patients display distinct GM profiles that may alter therapeutic responses. This comprehensive review synthesizes current literature on the interplay between KD and GM in GBM, highlighting mechanisms by which GM variability affects metabolic outcomes. Understanding these interactions is essential to reconcile discrepant findings and optimize patient selection for KD-based interventions, ultimately advancing personalized metabolic strategies in neuro-oncology. © 2026 Taylor & Francis Group, LLC.