Fecal Microbiota Transplantation Attenuates COPD by Regulating the MMP-9/TIMP-1 Pathway

Background Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide, with limited therapeutic options beyond symptom control. Airway remodeling driven by imbalance of the MMP-9/TIMP-1 axis is central to COPD progression. While fecal microbiota transplantation (FMT) has shown promise in immune regulation, its therapeutic potential and mechanism in COPD remain undefined. We aimed to determine whether FMT alleviates COPD by modulating the MMP-9/TIMP-1 signaling pathway. Methods Using an in vivo mouse model was established using cigarette smoke exposure and intratracheal lipopolysaccharide. Following model induction, rats received daily intragastric FMT for four weeks. Lung pathology, MMP-9/TIMP-1 expression, inflammatory cytokines, immune cell subsets, and gut microbiota diversity were analyzed. Results COPD model rats exhibited severe airway injury, upregulated MMP-9/TIMP-1 signaling, heightened inflammation, and reduced microbial diversity. FMT treatment significantly attenuated airway remodeling, restored MMP-9/TIMP-1 balance, reduced inflammatory cytokine levels, rebalanced Th17/Treg cells, and improved gut microbiota richness and diversity. Conclusion Our findings demonstrate for the first time that FMT can ameliorate COPD by suppressing MMP-9/TIMP-1–mediated airway remodeling through modulation of the gut–lung axis. This work highlights FMT as a novel therapeutic strategy with mechanistic insight into its role in COPD treatment.