A Comprehensive Microbial Gene Catalog of the Human Airway Microbiome Across Anatomical Sites and Geographic Regions

The respiratory microbiota is a critical determinant of airway health, yet functional characterization remains challenging due to the lack of a high-resolution reference catalog. To address this gap and enable systematic investigation at both species and gene levels, we constructed the integrated Human Airway Microbiome Gene Catalog (iHAMGC) through high-throughput metagenomic analysis of 12,273 airway samples. This catalog comprises 24,185,985 non-redundant microbial genes and provides extensive taxonomic and functional annotations, with a particular focus on clinically relevant elements, including antibiotic resistance genes, virulence factors, and antimicrobial peptides. We further resolved the bacterial hosts of resistance genes and virulence factor genes, as well as taxa contributing to antimicrobial peptide activity. The iHAMGC captures site-specific microbial and functional variations across distinct airway niches and reveals regional differences in functional potential. By offering a comprehensive, publicly accessible reference for airway microbial genes, the iHAMGC serves as a foundational resource for advancing our understanding of the airway microbiota in respiratory health and disease.