Each year in the United States, over 200,000 patients receive radiation therapy to treat brain metastases. Stereotactic radiosurgery (SRS) is a non-invasive radiation therapy procedure that uses targeted radiation beams to treat brain pathologies. With the rising popularity of SRS as a lower-risk treatment option for intracranial conditions as opposed to surgery, the incidence of adverse radiation effects (ARE) has increased, with 20% of radiotherapy patients developing radiation necrosis (RN) post-treatment. RN is difficult to identify and diagnose radiographically and can become symptomatic and even life-threatening. A previous experiment we conducted investigated the role of gut microbiome modulation on AREs. Compared to the control, mice pre-treated with antibiotics developed fewer brain lesions, and metabolomic analysis showed elevated tryptophan (TRP) derived  metabolite levels in their plasma. TRP is thought to modulate AREs through the gut-brain axis. The gut microbiota can regulate the metabolism of TRP, affecting the TRP metabolites that enter the central nervous system via the blood-brain barrier. This study aims to determine whether gut-derived TRP metabolites are the mechanistic link mediating radioprotective effects in a murine model. TRP metabolites were administered to C57BL/6 mice via oral gavage and intraperitoneal injection to be tested for radioprotective effects compared to a control group. Using the X-Rad 225CX  small animal irradiator system, mice were stereotactically irradiated  and cone-beam CT scans obtained to identify and assess AREs lesion formation. The brains were then harvested for Evan’s Blue and Hematoxylin and Eosin analysis to observe histopathologic changes and integrity of the blood brain barrier. We hypothesize that gut microbiota TRP metabolites are involved in radioprotection by minimizing/preventing AREs due to their role in neuroinflammation through the gut-brain axis (GBA). This study aims to provide insights into gut microbiota TRP metabolism and the GBA that could advise future clinical AREs treatment.