Clostridium butyricum attenuates radiation-induced bone loss through gut microbiota and immune regulation in mice.

Radiation-induced bone loss remains clinically challenging due to limitations of existing treatments. Using a mouse model of fractionated total abdominal irradiation (TAI), we demonstrate that TAI triggers severe osteoporosis characterized by trabecular bone loss, suppressed osteogenesis, and elevated osteoclast activity. Through 16S rRNA sequencing and immune profiling, we found TAI induced gut dysbiosis, immune dysregulation such as Th17/Treg imbalance, and systemic inflammation. Oral supplementation with C. butyricum reversed bone loss, activated osteogenic signaling, suppressed osteoclastogenesis, and rebalanced T-cell subsets in mice. Crucially, it restored gut microbiota composition and attenuated inflammation in intestinal and bone marrow microenvironments. Our findings establish C. butyricum as a gut microbiota-targeted therapy for radiation-induced bone loss via the gut-immune-bone axis.