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Introduction: The homeostasis of the microbiome in lower respiratory tract is crucial in sustaining normal physiological functions of the lung. Different pulmonary diseases display varying degrees of microbiome imbalance; however, the specific variability and clinical significance of their microbiomes remain largely unexplored. Methods: In this study, we delineated the pathogen spectrum and commensal microorganisms in the lower respiratory tract of various pulmonary diseases using metagenomic sequencing. We analyzed the disparities and commonalities of the microbial features and examined their correlation with disease characteristics. Results: We observed distinct pathogen profiles and a diversity in lower airway microbiome in patients diagnosed with cancer, interstitial lung disease, bronchiectasis, common pneumonia, Nontuberculous mycobacteria (NTM) pneumonia, and severe pneumonia. Discussion: This study illustrates the utility of Metagenomic Next-generation Sequencing (mNGS) in identifying pathogens and analyzing the lower respiratory microbiome, which is important for understanding the microbiological aspect of pulmonary diseases and essential for their early and precise diagnosis. [ABSTRACT FROM AUTHOR]