Lung Microenvironment Among Patients with Nontuberculous Mycobacterial Pulmonary Disease by Metagenomic Sequencing...

Background: Nontuberculous mycobacterial pulmonary disease (NTM-PD) is an increasingly prevalent chronic infection, where the host immune status plays a crucial role in disease susceptibility and progression. The complex pulmonary microenvironment, characterized by diverse microbial communities and host immune interactions, exhibits distinct features that may be fundamentally altered by the patient's underlying immune state. Methods: A total of 111 sputum specimens and 64 bronchoalveolar lavage fluid (BALF) specimens were collected from 143 patients diagnosed with NTM-PD under different immune states. Metagenomic sequencing was performed on these specimens to characterize and compare the pulmonary microenvironmental features among NTM-PD patients with a distinct immune status through comprehensive bioinformatic analyses. Results: The immunosuppressed group exhibited a lower α-diversity in sputum specimens (p < 0.05). Principal Coordinates Analysis (PCoA) of β-diversity for sputum and BALF specimens revealed significant differences between the groups (p < 0.05). Linear discriminant analysis Effect Size (LEfSe) analysis identified species enriched in the immunosuppressed group. A co-occurrence network analysis indicated that the immunosuppressed group had more structured and actively connected networks compared to the control group. The Mantel test confirmed that the abundance of these species enriched was associated with clinical immune-inflammation-related indicators in patients. Conclusions: Our study reveals the pulmonary microenvironment in immunosuppressed patients with NTM-PD. Further work is required to explore the two-way relationship between micro-organisms and immune and inflammatory responses, with the influence on patient outcomes.