Microbiome-host interactions Involve in the Pathogenesis of Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A cross-sectional study

Abstract

Background Chronic Obstructive Pulmonary Disease (COPD) exhibits heterogeneity in clinical symptoms and phenotypes, and microbiome-host interactions play a crucial role in it. Our study aims to explore the potential mechanisms airway microbiome contributed to the acute exacerbation of COPD, so as to prepare for further research and intervention of COPD. Methods We enrolled 31 acute exacerbation stage and 26 stable stage COPD patients to collect their sputum samples for metagenomic and RNA sequencing, identify distinguished microbiome and different expressed genes (DEGs) to conduct bioinformatic analysis and clinical correlation analysis. Results In genus level, Fusobacterium (p < 0.001), Haemophilus (p = 0.007) expressed higher in acute exacerbation stage while Moraxella (p = 0.039), Rothia (p = 0.032) and Granulicatella (p = 0.018) in the stable stage. In species level, Rothia mucilaginosa (p = 0.015) up-regulated in acute exacerbation stage and Haemophilus influenzae (p = 0.015) up-regulated in stable stage. DEGs enriched significantly in “type I interferon signaling pathway” (adjusted p = 0.001) and “defense response to virus” (adjusted p = 0.023) in GO enrichment analysis. 5 remarkable upregulated pathways were detected when DEGs were analyzed in KEGG PATHWAY database, which were “Influenza A” (p < 0.001, q = 0.012), “Herpes simplex infection” (p < 0.001, q = 0.014), “Cytosolic DNA-sensing pathway” (p = 0.002, q = 0.024), “Toll-like receptor signaling pathway” (p = 0.006, q = 0.045), and “TNF signaling pathway” (p = 0.006, q = 0.045). 10 DEGs were screened as hub genes for further exploration. Besides, we found the hub gene OASL had a positive correlation with CAT score (r = 0.34, p < 0.05). Conclusions Haemophilus influenzae and Moraxella regulate the pathogenesis of AECOPD through type I IFNs and TLRs signaling pathways, and Rothia, a commonly considered anti-inflammatory bacteria, could be a valuable therapeutic target in COPD. Meanwhile, 9 hub genes were screened for further research as well.