Deciphering the microbial landscape of lower respiratory tract in health and respiratory diseases

Cheng, C.; Li, Y.; Wang, S.; Wang, H.; Liu, D.; Wang, Q.; Che, Y.; Xue, L.; Chao, N.; He, X.; Li, C.; Tian, H.; Zhou, J.; Wang, X.; Yang, Y.; Zhu, Y.; Xu, R.; Wang, Z.; Li, W.

doi:10.1101/2025.06.11.659233

bioRxiv · 10.1101/2025.06.11.659233

Deciphering the microbial landscape of lower respiratory tract in health and respiratory diseases

Cheng, C.·Li, Y.·Wang, S.·Wang, H.·Liu, D.·Wang, Q.·Che, Y.·Xue, L.·Chao, N.·He, X.·Li, C.·Tian, H.·Zhou, J.·Wang, X.·Yang, Y.·Zhu, Y.·Xu, R.·Wang, Z.·Li, W.

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Abstract

The microbiota plays an important role in maintaining lung homeostasis and the development of respiratory diseases. However, there have not been detailed characteristics of lung microbiome in health and respiratory diseases. Bronchoalveolar lavage fluid of 43 healthy individuals, 23 COVID patients, and 28 non-small cell lung cancer patients was conducted to characterize microbial diversity and function by metagenomic sequencing. We identified 196 species in health lung after removing low abnudance species. The most abundant species were Staphylococcus aureus, Salmonella enterica, and Klebsiella pneumoniae. Keystone species were identified through co-network analysis, such as Granulicatella adiacens and Mogibacterium diversum. To further explore the microbial function in the healthy lung, we obtained 56 non-redundant metagenome-assembled genomes (MAGs) and subsequently classified them into nine phyla. Metabolism and genetic information processing exhibit high abundance, including bacterial secretion systems, protein export, and Staphylococcus aureus infection, indicating a close correlation between microbiota and the host. Furthermore, the microbiome pairwise distances of non-small cell lung cancer (NSCLC) participants were more similar to those of the healthy group than those of individuals with COVID-19. Rothia dentocariosa, Corynebacterium kefirresidentii, Sphingobium yanoikuyae were enriched in the healthy group, while Schaalia odontolytica, Actinomyces graevenitzii, and Rothia mucilaginosa was enriched in the NSCLC group. Overall, this study provides a comprehensive overview of the diversity and gene function of the lung microbiome, which will facilitate future studies of microbiota associated with respiratory diseases in humans.

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Cheng, C., Li, Y., Wang, S., Wang, H., Liu, D., Wang, Q., Che, Y., Xue, L., Chao, N., He, X., Li, C., Tian, H., Zhou, J., Wang, X., Yang, Y., Zhu, Y., Xu, R., Wang, Z., Li, W.. 2025-06-13. Deciphering the microbial landscape of lower respiratory tract in health and respiratory diseases. https://doi.org/10.1101/2025.06.11.659233

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