Table 2.

Therapeutic targeting of the microbiome-mitochondria axis in neuro-oncology.

Therapeutic strategy	Specific intervention/example	Microbiome-mitochondria connection	Potential therapeutic outcome	Evidence base/translational status	Key references
Microbiome modulation • Microbial metabolite targeting	Dietary interventions, prebiotics, probiotics, synbiotics, FMT SCFAs, particularly butyrate; tryptophan-derived metabolites	Modifies microbial composition and metabolite production, potentially influencing host metabolism and mitochondrial signaling Microbial metabolites regulate mitochondrial metabolism, redox signaling and immune-cell function	Immune and metabolic reprogramming; improved treatment responsiveness Modulation of tumor growth, inflammation and immune surveillance	Preclinical; emerging clinical evidence Mainly preclinical	(Chen et al., 2025; Green et al., 2024)
Mitochondrial targeting • Mitochondrial quality control	OXPHOS/ETC inhibition, mitochondrial ROS and metabolic targeting Mitophagy and mitochondrial dynamics/transfer	Intersects with microbial metabolite and nutrient availability Mitochondrial adaptation may be influenced by cellular and metabolic signals	Impaired tumor bioenergetics and increased metabolic stress Impaired tumor bioenergetics and increased metabolic stress	Preclinical/early translational Preclinical	(Liang et al., 2025; Chung et al., 2025; Liang et al., 2025; Storevik et al., 2026)
Immunometabolic targeting	Glycolysis, glutaminolysis, lactate and myeloid-cell metabolism	Microbial metabolites can influence tumor-immune metabolic interactions	Reduced immunosuppression and enhanced antitumor immunity	Preclinical/early translational	(Gao et al., 2025; Yang et al., 2025)
Combination therapy	Microbiome modulation + immune checkpoint blockade/metabolic therapy	Simultaneous manipulation of microbial, immune and metabolic pathways	Potential to overcome treatment resistance	Emerging clinical/preclinical	(Weathers et al., 2025; Liang et al., 2025; Chung et al., 2025)
Personalized approaches	Microbiome + metabolomic + tumor/immune profiling	Identifies patient-specific microbial and mitochondrial/metabolic phenotypes	Treatment stratification and individualized therapy	Early translational/future	(Chen et al., 2025; Weathers et al., 2025; Green et al., 2024)