RBIO-03. BENEFICIAL CLOSTRIDIUM SPP ORAL SUPPLEMENTATION MITIGATES RADIATION-INDUCED COGNITIVE DYSFUNCTION WITH GUT MICROBIOTA MODULATION IN RICD MICE

Abstract Radiation therapy (RT) a critical treatment for brain tumors; often leads to radiation-induced cognitive dysfunction (RICD), which significantly impacts patients' quality of life. The gut microbiome and its metabolites play a crucial role in regulating CNS function, RT disturbs the balance of the gut microbiota causing dysbiosis (imbalance in beneficial microorganisms), and Gut-dysbiosis have been linked to various cognitive disorders. This study aims to investigate the effects of RT on the gut-microbiome and cognitive function, C57BL/6 mice were exposed to Sham/9Gy/15Gy cranial irradiation and conducted cognitive tests using the Y-maze and Novel Object Recognition Test at different time points. Both 9Gy and 15Gy irradiation led to significant cognitive dysfunction at 10 and 30 days post-irradiation. We collected fecal samples before RT and at 10 and 30 days after RT to extract microbial DNA. The 16S rRNA gene was sequenced and analyzed using the ATIMA visualization toolkit. By comparing pre-irradiation samples with samples at 10 and 30 days post-irradiation, we observed significant gut dysbiosis in both 9Gy and 15Gy irradiated mice. The 15Gy group exhibited more pronounced and consistent changes in fecal microbiome diversity following RT. Notably, the Clostridium group at the order, family, and genus levels consistently decreased in the 15Gy irradiated mice. Certain Clostridium species are known as major producers of Short Chain Fatty Acids (SCFAs) in the gut. Based on this, we hypothesized that oral supplementation with beneficial SCFA-producing bacteria could ameliorate RICD. To test this hypothesis, a separate group of mice received 15Gy RT along with oral gavage containing a cocktail of Clostridium strains. After a 20-day post-irradiation, cognitive tests revealed that the group supplemented with Clostridium spp exhibited significantly improved cognitive performance. Our findings suggest that gut dysbiosis may contribute to RICD, and oral supplementation of SCFA-producing bacteria could be a potential strategy to mitigate RICD.