Gut–Lung Crosstalk: Correlating Gut Microbial Composition with Pulmonary Disorders in COPD Murine models

Background Chronic Obstructive Pulmonary Disease (COPD) is a systemic inflammatory disease with significant extrapulmonary manifestations. The gut-lung axis has emerged as a crucial area of research, but the specific alterations in the gut microbiota and their correlation with COPD pathophysiology remain largely unknown. Methods We established a murine model of COPD by exposing SD rats to chronic cigarette smoke (CS) and further induced COPD exacerbation (ECOPD) using PM2.5 and LPS. We characterized the gut microbiota using 16S rRNA gene sequencing and performed comprehensive bioinformatics analysis, including alpha and beta diversity, compositional analysis, differential species analysis (LEfSe), and functional prediction (KEGG). We also assessed lung function, lung histopathology, and inflammatory markers to validate the COPD model and investigate correlations with gut microbiota alterations. Results The COPD murine model successfully recapitulated key features of the disease, including airflow limitation, lung inflammation, and alveolar destruction. We observed significant decreases in gut microbial richness and diversity in COPD animals except the LPS-induced ECOPD ones, characterized by alpha diversity analysis. A general shift was observed in microbial taxa for COPD animals compared to controls, specifically an increase in Erysipelotrichaceae and Bifidobacteriaceae , and a decrease in Lactobacillaceae and Lachnospiraceae , and the exacerbation triggers (PM2.5 and LPS) further modify the gut microbiota structure. Importantly, we found significant correlations between gut microbial diversity and lung function, as well as between specific bacterial genera and pulmonary inflammatory markers. Functional prediction analysis indicated significant alterations in metabolic pathways within the gut microbiota of COPD animals. Conclusion Our study demonstrates that a murine model of COPD exhibits significant gut microbiota dysbiosis, which is closely correlated with key pulmonary pathophysiological indicators. These findings provide novel evidence for the involvement of the gut-lung axis in COPD and suggest that the gut microbiota may serve as a potential diagnostic biomarker and therapeutic target for this debilitating disease.