BALF Metagenomic Sequencing Maps Lower-Airway Microbial Shifts in Tuberculosis

Patients with pulmonary tuberculosis harbor a measurably different mixture of microbes in their lower airways than patients undergoing bronchoscopy for other pulmonary diseases, according to a metagenomic sequencing study conducted at Tianjin Haihe Hospital and Haihe Clinical School of Tianjin Medical University in China. The work, accepted for publication in Frontiers in Cellular and Infection Microbiology, applied metagenomic next-generation sequencing to bronchoalveolar lavage fluid in order to characterize the microbial communities present alongside the Mycobacterium tuberculosis complex in the deep lung. The research team, led by Hongxia Shao, Huaiyong Chen, Wanjie Yang and Junping Wu, collected bronchoalveolar lavage fluid, the fluid obtained when a bronchoscope is used to wash and sample the lower airways.

Rather than testing for one organism at a time, metagenomic next-generation sequencing reads the genetic material of the microbes present in the sample, allowing the researchers to profile the bacterial and fungal taxa in each specimen using standard bioinformatics tools that measure diversity, composition and relative abundance. Pulmonary tuberculosis is caused by the Mycobacterium tuberculosis complex, and the comparison group consisted of patients with a heterogeneous mix of non-tuberculosis pulmonary conditions, so the analysis contrasted the tuberculosis airway microbiome against that of a clinically varied control population. Samples from patients with pulmonary tuberculosis showed higher Shannon and Simpson indices, two widely used within-sample diversity metrics, than samples from the non-tuberculosis group.

Richness, which counts the number of distinct taxa present without weighting them by evenness, did not differ significantly between the two groups. That combination of findings indicates that the tuberculosis samples did not simply contain more types of microbes than the comparison samples. Instead, the higher diversity indices alongside unchanged richness suggest that the difference lies in how the taxa already present are distributed, with a broader range of organisms reaching detectable relative abundances in the tuberculosis airway environment.

Beta diversity analyses, which compare the overall composition of microbial communities between samples, revealed modest but statistically detectable differences in community composition between the pulmonary tuberculosis and non-tuberculosis groups. The authors characterize the signal as a difference in community structure rather than a wholesale shift, but it was sufficient to distinguish the two clinical populations in the sequencing data. When the researchers examined which taxa drove those compositional differences, the tuberculosis group showed higher relative abundances of the Mycobacterium tuberculosis complex itself, together with several oral-associated taxa, including the genera Prevotella and Fusobacterium.

The non-tuberculosis group, by contrast, showed higher relative abundances of other organisms, including the bacterium Pseudomonas aeruginosa and the fungus Aspergillus fumigatus. The authors frame the results as a description of compositional differences between the two groups, not as evidence of any causal role for the individual microbes in either disease state. The modest size of the beta-diversity signal and the heterogeneity of the non-tuberculosis group also limit how broadly the findings can be generalized.

Even so, by characterizing the lower-airway microbial ecology of pulmonary tuberculosis with an unbiased sequencing method, the work adds a reference point for understanding pulmonary microbial ecology in tuberculosis and identifies differences in microbial community composition and structure between patients with the disease and patients with other pulmonary conditions.

Subject of Research: Characterization of lower-airway microbial communities in pulmonary tuberculosis by BALF metagenomic sequencing

Article Title: Characterization of lower-airway microbial communities in pulmonary tuberculosis by BALF metagenomic sequencing

Article References: Shao, H., Li, X., Miao, X., Tang, L., Gu, Y., Qin, Z., Han, J., Li, J., Wang, Q., Yang, W., Chen, H., & Wu, J. (2026). Characterization of lower-airway microbial communities in pulmonary tuberculosis by BALF metagenomic sequencing. Frontiers in Cellular and Infection Microbiology, 16, Article 1938581. https://doi.org/10.3389/fcimb.2026.1938581

Image Credits: AI Generated

DOI: 10.3389/fcimb.2026.1938581

Keywords: Characterization, lower-airway, microbial, communities, pulmonary, tuberculosis, BALF, metagenomic, sequencing, scientific research