Intermittent hypoxia drives lung microbiome-metabolome remodeling to create a pro-inflammatory landscape in murine...

Obstructive sleep apnea-hypopnea syndrome (OSAHS), characterized by intermittent hypoxia (IH), is associated with pulmonary complications. The specific mechanisms by which IH impacts the lung's native microbiome and its functional metabolic output, however, remains largely uncharted.

We established an OSAHS model in C57BL/6J mice using 4 weeks of IH exposure. Lung histology and inflammatory cytokines in bronchoalveolar lavage fluid (BALF) were assessed. We performed an integrated analysis of the lung microenvironment using 16S rRNA sequencing for the microbiota and LC-MS for the metabolome.

IH induced significant lung inflammation, evidenced by inflammatory infiltration and a polarized cytokine profile (elevated IL-1β, IL-6, TNF-α; decreased IL-10). Microbiome analysis revealed IH-driven dysbiosis, characterized by a marked shift in community structure and enrichment of pro-inflammatory taxa (e.g., Bacillota, Mycoplasma). Concurrently, metabolomic profiling uncovered widespread disturbances, with significant alterations in 500 metabolites. Key changes included rises in pro-inflammatory molecules (e.g., stachydrine) and falls in protective mediators (e.g., prostaglandin E2, embelin). Pathway analysis indicated these metabolites were enriched in niacin metabolism, inflammatory mediator regulation of TRP channels, and neuroactive ligand-receptor interactions. Crucially, correlation analysis delineated a robust interplay between the specific IH-altered microbial taxa and the disturbed metabolic pathways, suggesting a coordinated microenvironmental response.

Our integrated analysis reveals a compelling association between the lung microbiota and metabolome, suggesting their potential role as a cooperative factor associated with pulmonary inflammation in OSAHS. This study establishes a valuable resource and outlines a framework for future mechanistic and therapeutic exploration.