Oral Microbial Metabolite Confers Protection Against Radiation-Induced Mucosal Injury

This study investigates how radioresistant Deinococcus geothermalis (Dg) suppress radiation-induced mucosal injury (RIMI) through its metabolite urocanic acid, addressing a critical gap in active intervention strategies. Clinical saliva sample from 80 patients receiving head and neck radiotherapy from 2024.8-2024.12 (ages 50-70, Ethics Approval KQ-YJ-2024-161) were analyzed. BALB/c mice (n=140, male, Ethics Approval kq-066) were used for modeling and mechanistic exploration. Methods included 16S rRNA sequencing, NLRP3 inflammasome assays, and pyroptosis quantification via caspase-1/GSDMD activation. Statistical significance was determined by ANOVA (p<0.05). The relative abundance of Deinococcus geothermalis (Dg) was negatively associated with the severity of radiation-induced oral mucositis. In vitro, urocanic acid suppressed NLRP3-dependent pyroptosis following radiation exposure. Furthermore, urocanic acid administration ameliorated radiation-associated mucosal damage in both oral and colonic tissues of murine models. This study pioneers the role of radioresistant commensals in RIMI protection, establishing urocanic acid as a novel therapeutic agent to actively mitigate radiation toxicity, advancing precision radioprotection strategies.