Fecal Microbiota Transplantation Restores Gut Homeostasis and Enhances ER-Phagy to Mitigate Radiation-Induced Lung Injury

Radiation-induced lung injury (RILI) is a severe side effect of radiation therapy, characterized by lung tissue damage, inflammation, and organ dysfunction. Although fecal microbiota transplantation (FMT) has shown potential in alleviating radiation-induced damage, its underlying mechanisms remain unclear. This study aims to explore the effects of FMT on RILI, focusing on gut microbiota changes, metabolic alterations, and the endoplasmic reticulum (ER) adaptive responses. Using a total lung irradiation (TLI) mouse model, we found that FMT effectively mitigated lung tissue damage, reduced collagen deposition, and alleviated inflammation, as confirmed by histological analysis and serum cytokine measurements. Notably, FMT restored the gut microbiota imbalance caused by radiation exposure, promoted gut motility, and enhanced intestinal barrier function. Metabolomics analysis revealed thatTLI significantly disrupted the metabolism of unsaturated fatty acids and arachidonic acid, whereas FMT partially restored these metabolic pathways. Multi-omics analysis further uncovered the contribution of gut microbiota to various metabolites and the key associations between specific metabolites and ER-phagy-related genes.