Fecal microbiota transplantation alleviates sepsis-induced acute lung injury by improving mitochondrial function.

Sepsis-induced acute lung injury (ALI) remains a critical clinical challenge with limited therapeutic options. This study investigated the protective effects and underlying mechanisms of fecal microbiota transplantation (FMT) in a murine model of sepsis-induced ALI. 16S rRNA sequencing confirmed that FMT rescued sepsis-induced gut microbiota dysbiosis, restoring microbial diversity and composition. The results demonstrated that FMT significantly improved survival, attenuated pulmonary pathological damage and edema, and reduced systemic and pulmonary levels of proinflammatory cytokines (TNF-α, IL-6, and IL-1β). Furthermore, FMT preserved alveolar-capillary barrier integrity, as evidenced by reduced vascular permeability and upregulated expression levels of tight junction proteins (ZO-1 and occludin). Mechanistically, FMT ameliorated mitochondrial dysfunction in lung tissue, as evidenced by the restoration of oxidative phosphorylation capacity, increased ATP production, reduced mitochondrial reactive oxygen species accumulation, and decreased mitochondrial DNA release. These improvements were associated with a rebalancing of mitochondrial dynamics, characterized by increased expression levels of fusion proteins (OPA1, Mfn1, and Mfn2) and decreased expression of a fission protein (Drp1). Our findings highlight the gut-lung axis as a therapeutic target in sepsis and demonstrate that FMT alleviates sepsis-induced ALI by restoring gut microbiota homeostasis and subsequently preserving mitochondrial function. Further clinical studies are warranted to validate these preclinical findings and explore optimal FMT protocols for critical care applications.