Review frames microbiome–mitochondria crosstalk in glioblastoma research

A review proposes that signals from gut microbes and mitochondrial activity may form a biological axis connecting metabolism, immunity and glioblastoma, while emphasizing that a causal role in human brain tumors remains unproven. The framework focuses on how microbiome-derived compounds could influence immune responses, barrier function, cellular metabolism and neural signaling, and how mitochondria may translate those signals into changes in energy production, reactive oxygen species, calcium communication, mitochondrial biogenesis, quality control and apoptosis.

The microbial signals examined in the review include short-chain fatty acids, bile acid metabolites, tryptophan metabolites and other microbial compounds. Their effects on barrier function, immunity, metabolism and neural signaling provide the proposed entry point for microbiome–mitochondria crosstalk. Rather than reporting a clinical trial, the review assembles a mechanistic framework for interpreting how intercellular signals might affect intracellular mitochondrial processes in the context of neuro-oncology.

In glioblastoma, the proposed axis may be relevant to several aspects of tumor metabolic plasticity. The review considers links with glycolysis, oxidative phosphorylation, amino- and lipid-metabolic adaptations, mitochondrial transfer and adaptation to hypoxia. It also examines possible relationships with tumor-cell stemness and immune suppression in the tumor microenvironment, as well as interactions between microbiome-derived cues, mitochondria and tumor-associated immune populations. These are proposed connections and research questions, not demonstrated effects of a particular metabolite in patients.

The review identifies microbiome-derived and mitochondrial biomarkers as possible targets for investigation, alongside multi-omics approaches, single-cell technologies, spatial biology, artificial intelligence and new experimental models. Such tools could help researchers identify signatures relevant to the proposed axis. Modulating the microbiome, mitochondrial processes or both through combination approaches also appears promising, but the supplied evidence does not establish efficacy, a safe regimen or clinical benefit in glioblastoma. Prospective and mechanistic studies are therefore needed to test whether microbiome-derived signals influence tumor mitochondrial biology, immunity and treatment-related biology in humans.

Subject of Research: Review of microbiome–mitochondria crosstalk in glioblastoma metabolism and immunity

Article Title: Microbiome-mitochondria crosstalk in neuro-oncology: molecular mechanisms, immunometabolic reprogramming, and therapeutic opportunities

Article References: Dash, D., Rajak, M., Manothiya, P., & Koiri, R. K. (2026). Microbiome-mitochondria crosstalk in neuro-oncology: molecular mechanisms, immunometabolic reprogramming, and therapeutic opportunities. Frontiers in Microbiomes, 5, Article 1983174. https://doi.org/10.3389/frmbi.2026.1983174

Image Credits: AI Generated

DOI: 10.3389/frmbi.2026.1983174

Keywords: glioblastoma, gut microbiome, mitochondrial biology, microbial metabolites, tumor metabolism, cancer immunity, metabolic plasticity, neuro-oncology, multi-omics, biomarkers, Microbiome-mitochondria, crosstalk