Electroacupuncture modulates gut-lung microbiota and lung EMT to attenuate airway remodeling in COPD.

Abstract

<p>BACKGROUND: Chronic obstructive pulmonary disease (COPD) airway remodeling is primarily driven by epithelial-mesenchymal transition (EMT), which is exacerbated by gut-lung axis (the bidirectional communication between gut and lung microbiota) dysbiosis and systemic inflammation. Although electroacupuncture (EA) demonstrates therapeutic potential in COPD, its mechanisms in modulating the gut-lung axis to alleviate inflammation and EMT remain unclear. METHODS: In cigarette smoke and lipopolysaccharide (LPS)-induced COPD rats, we evaluated lung function, airway collagen deposition, pro-inflammatory and anti-inflammatory cytokines in serum, bronchoalveolar lavage fluid (BALF), and colon tissue, EMT markers in lung tissue, serum LPS levels, and 16S rRNA sequencing of lung and gut microbiota. Interventions comprised authentic EA at bilateral "Feishu" (BL13) and "Zusanli" (ST36) acupoints versus sham acupuncture at non-acupoint. RESULTS: Electroacupuncture significantly attenuated airway remodeling, as evidenced by improved lung function and reduced collagen deposition. EA modulated gut-lung microbiota by suppressing pro-inflammatory pathogens and enriching immunoregulatory taxa. These changes correlated with reduced serum endotoxemia and inflammation, marked by decreased pro-inflammatory cytokines and increased IL-10 in serum, BALF, and colon tissues. The ameliorated inflammatory environment was further linked to inhibition of EMT in airways, shown by upregulated epithelial markers and downregulated mesenchymal markers. Correlative analyses supported these associations. Ligilactobacillus enrichment negatively correlated with serum LPS, while Mycoplasmopsis positively associated with inflammation and EMT markers. Sham acupuncture failed to achieve these effects. CONCLUSION: Electroacupuncture ameliorates airway remodeling in COPD by modulating gut and lung microbiotareducing inflammation and inhibits EMT, suggesting microbiota regulation as a potential contributor to its therapeutic effects.</p>