Sex differences in fecal microbiota transplantation for mitigating radiation-induced thrombocytopenia in mice: efficacy amplified by inulin

BACKGROUND: Fecal microbiota transplantation (FMT) shows potential in promoting hematopoiesis, with efficacy influenced by donor sex. However, its role in radiation-induced thrombocytopenia (RIT) and its sex-specific effects remain unclear. While inulin may enhance FMT efficacy, this has not been explored in the context of RIT. METHODS: We established an irradiation-induced thrombocytopenia (RIT) model in male and female mice via 4 Gy X-rays exposure. FMT was administered orally as a fecal suspension. Platelet recovery was monitored via hematology analyzer, megakaryopoiesis was assessed by flow cytometry and H&E staining; gut microbiota changes were evaluated by 16S rRNA sequencing. RESULTS: abundance. Furthermore, transplanting feces from female donors also accelerated platelet recovery in irradiated male mice, whereas feces from male donors does not. INU selectively enriched probiotic colonization, thereby fostering a favorable microbial structure that enhanced FMT efficacy. CONCLUSIONS: The sexually dimorphic gut microbiota contributes to sex-specific FMT efficacy in alleviating radiation-induced thrombocytopenia, which can be further amplified by inulin. This study offers sex-specific microbial therapy for radiation-induced thrombocytopenia and a prebiotic-based strategy to boost FMT efficacy.