Sex-dependent protective responses of taurine in ameliorating radiation-induced intestinal injury: gut microbiota reprogramming in males and estrogen-dependent immunity in females

Radiation-induced intestinal injury (RIII) limits abdominal and pelvic radiotherapy. Safe and effective radioprotectors that do not protect tumors remain an unmet need. Here, we examined the radioprotective effect of taurine (Tau) in mice subjected to whole-abdominal irradiation (WAI) and whether this effect depends on sex. Tau treatment improved post-irradiation survival, preserved intestinal stem cells, prevented mucosal barrier breakdown, and reduced systemic inflammation. These effects, however, were sex-dependent. In male mice, Tau altered the gut microbiota, increasing Ligilactobacillus abundance and shifting arginine and proline metabolism. In female mice, Tau maintained circulating estrogen levels, which in turn upregulated AICDA expression and enhanced IgA-mediated intestinal immunity. Under the specific dosing regimens and radiation parameters utilized in this study, Tau neither altered baseline tumor progression nor compromised the tumor response to irradiation. We conclude that Tau protects against RIII through sex-specific mechanisms, microbiota reprogramming in males and estrogen-AICDA-IgA signaling in females, without compromising the antitumor efficacy of radiotherapy.