Glioma and the gut-brain axis: opportunities and future perspectives

Abstract

The gut-brain axis has presented a valuable new dynamic in the treatment of cancer and central nervous system (CNS) diseases. However, little is known about the potential role of this axis in neuro-oncology. The goal of this review is to highlight potential implications of the gut-brain axis in neuro-oncology, in particular gliomas, and future areas of research. The gut-brain axis is a well-established biochemical signaling axis that has been associated with various CNS diseases. In neuro-oncology, recent studies have described gut microbiome differences in tumor-bearing mice and glioma patients compared to controls. These differences in the composition of the microbiome are expected to impact the metabolic functionality of each microbiome. The effects of antibiotics on the microbiome may affect tumor growth and modulate the immune system in tumor-bearing mice. Preliminary studies have shown that the gut microbiome might influence PD-L1 response in glioma-bearing mice, as previously observed in other non-CNS cancers. Groundbreaking studies have identified intratumoral bacterial DNA in several cancers including high-grade glioma. The gut microbiome and its manipulation represent a new and relatively unexplored area that could be utilized to enhance the effectiveness of therapy in glioma. Further mechanistic studies of this therapeutic strategy are needed to assess its clinical relevance.

Keywords: fecal metabolites; glioblastoma; glioma; gut microbiome; gut–brain axis.

Figure 1.

Factors known to influence the gut microbiome composition.

Figure 2.

The gut–brain axis communication is bidirectional and mediated by several pathways. This communication is performed through hormonal (hypothalamic–pituitary–adrenal axis), metabolic (short-chain fatty acids and neurotransmitters), and immunologic pathways. Moreover, the gut microbiome interacts with the brain through the enteric nervous system and vagus nerve, which can be influenced either by the gut microbiota itself or indirectly through a local effect on the pathway by neuroactive compounds (eg, noradrenaline, serotonin, dopamine, tryptophan, and short-chain fatty acid).

Figure 3.

Glioma alters the gut microbiome, fecal metabolites, and immune system. Illustrative figure derived from animal model data. Tumor growth with consequent blood–brain barrier disruption changes the relative taxa abundance (decrease in Firmicutes phylum and increase in Verrucomicrobiota and Bacteroidetes phyla) in mice. Similar results were observed in humans compared to the control in the same study. Glioma-bearing mice have been identified to present a decrease in short-chain fatty acids and important neurotransmitters (5-hydroxindoloacetic acid and norepinephrine). Moreover, it has been shown that antibiotic treatment induces NK cell impairment in glioma-bearing mice.