Abstract
BACKGROUND: Glioblastoma (GB) is the most common subtype of glioma in adults. Despite treatment through tumor resection associated with chemo and radiotherapies, this cancer still has a very poor prognosis. Factors contributing to etiology, pathogenesis, or treatment resistance are not well known. The significance of understanding the microbiome-gut-brain axis (MGBA) in GB, a topic that has been recently shown to be crucial in several neurodegenerative diseases, cannot be overstated. Therefore, our project aims to understand how modulation of gut physiopathology (i.e., gut inflammation or microbiota dysbiosis) affects GB development and therapeutic resistance. MATERIAL AND METHODS: We have examined the relationship between gut inflammation, microbiome modulation, GB development, and therapeutic resistance. Mice received dextran-sulfate sodium (DSS), a gut pro-inflammatory agent, and were orthotopically injected with mGB2 GB cells. Some mice were then resected and treated by radio and chemotherapy using Temozolomide (TMZ). To understand the role of the gut microbiota in GB, we performed gut bacterial microbiota depletion using antibiotics. RESULTS: Our results showed that DSS-treated mice had a higher GB growth than non-treated mice. Moreover, the recurrence after treatment was higher in mice bearing gut inflammation. Interestingly, we also observed on DSS-treated mice that the GB-bearing mice had lower intestinal inflammation than the control. GB growth was also associated with microbiota modifications, which were restored by the treatment. Gut microbiota alteration leads to increased tumoral growth, suggesting an implication of the microbiota in GB development. CONCLUSION: Altogether, our results support the bidirectional communication between the gut and the brain in the context of GB. Alteration of gut physiopathology strongly impacts GB development and therapeutic resistance. This connection suggests that targeting the gut microbiome could slow down GB progression and/or improve treatment efficacy.