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Studies increasingly support the role of the gut microbiota in glioma development and treatment, although the exact mechanisms remain unclear. Research indicates that the gut microbiota can influence glioma progression, response to therapies, and the effectiveness of treatments like immunotherapy, with certain microbial compositions being linked to better outcomes. Additionally, the gut microbiota impacts the tumor microenvironment, affecting both tumor growth and the response to treatment. This review will explore glioma, the gut microbiota, and how their interaction shapes glioma development and therapy responses. Additionally, this review examines the influence of gut microbiota metabolites, such as short-chain fatty acids (SCFAs) and tryptophan, on glioma development and treatment. It also explores gut microbiome signaling via pattern recognition receptors, and the role of molecular mimicry between microbial and tumor antigens in glioblastoma, and if these interactions affect glioma development and treatment.

Along with the standard therapies for glioblastoma, patients are commonly prescribed trimethoprim-sulfamethoxazole (TMP-SMX) and dexamethasone for preventing infections and reducing cerebral edema, respectively. Because the gut microbiota impacts the efficacy of cancer therapies, it is important to understand how these medications impact the gut microbiota of patients. Using mice that have been colonized with human microbiota, this study sought to examine how TMP-SMX and dexamethasone affect the gut microbiome. Two lines of humanized microbiota (HuM) Rag1−/− mice, HuM1Rag and HuM2Rag, were treated with either TMP-SMX or dexamethasone via oral gavage once a day for a week. Fecal samples were collected pre-treatment (pre-txt), one week after treatment initiation (1 wk post txt), and three weeks post-treatment (3 wk post txt), and bacterial DNA was analyzed using 16S rRNA-sequencing. The HuM1Rag mice treated with TMP-SMX had significant shifts in alpha diversity, beta diversity, and functional pathways at all time points, whereas in the HuM2Rag mice, it resulted in minimal changes in the microbiome. Likewise, dexamethasone treatment resulted in significant changes in the microbiome of the HuM1Rag mice, whereas the microbiome of the HuM2Rag mice was mostly unaffected. The results of our study show that routine medications used during glioblastoma treatment can perturb gut microbiota, with some microbiome compositions being more sensitive than others, and these treatments could potentially affect the overall efficacy of standard-of-care therapy.