Fecal microbiota transplantation mitigates respiratory infection in rats exposed to hypobaric hypoxia by modulating the NLRP3 inflammasome and mucosal immunity

OBJECTIVE: To investigate the role of the gut-lung axis in respiratory infection under hypobaric hypoxia and the therapeutic potential of fecal microbiota transplantation (FMT). METHODS: Rats were exposed to hypobaric hypoxia (simulated 5000 m) for 14 days. Gut microbiota and serum short-chain fatty acids (SCFAs) were analyzed via 16S rRNA sequencing and GC-MS. Rats were then infected with Streptococcus pneumoniae and treated with FMT. Lung inflammation, NLRP3 inflammasome activity, cytokines, bacterial load, and secretory IgA (sIgA) were assessed. RESULTS: Hypobaric hypoxia triggered gut dysbiosis, marked by reduced abundance of Firmicutes D and Lactobacillus, elevated Bacteroidota, and decreased SCFA levels..FMT restored microbiota composition, increased acetic and butyric acid levels, and attenuated lung inflammation. FMT also enhanced NLRP3 inflammasome activation (NLRP3, ASC, Caspase-1), elevated IL-1β, IL-6, and TNF-α in BALF, reduced bacterial colonies, and increased airway sIgA in infected rats. CONCLUSIONS: FMT alleviates hypobaric hypoxia-aggravated respiratory infection by restoring gut microbiota, modulating SCFAs, and enhancing NLRP3-mediated mucosal immunity, highlighting the gut-lung axis as a therapeutic target.