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.<h4>Conclusions</h4>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. Here, CASP1 is linked to respiratory tract infectious disorder.