Dysbiosis associated with enhanced microbial mobility across the respiratory tract in pulmonary tuberculosis patients

The microbiota is actively engaged in interaction networks both with the host and among its own constituent members. However, comprehensive studies examining the microbiome profiles across various respiratory sites in pulmonary tuberculosis (PTB) are lacking. Here, we explored the diversity of the microbiome in PTB patients across multiple respiratory sites and investigated potential interactions between the microbiomes of these sites. A total of 130 respiratory tract samples were collected from multiple sites of 22 patients with PTB and 14 healthy individuals, including the oral cavity, trachea, and both the healthy and affected sides of the lungs. These samples were subjected to metagenomic sequencing to analyze the characteristics and diversity of the respiratory microbiome. We found that the respiratory tract of PTB patients had higher microbial diversity than seen in the healthy individuals (8,182 vs 6,465). Among them, Rothia, Prevotella and Actinomyces exhibited higher proportions in PTB. The characteristics of high diversity features in the oral site were more prominent with PTB, especially the notable difference of Rothia mucilaginosa. Additionally, Streptococcus, Neisseria, Prevotella and Fusobacterium have strong interactions with other species at present at various sites of PTB patients, as well as frequent communication between these species during migration in the upper and lower respiratory tract. The diversity and translocation of microbiota across the respiratory tract in PTB patients are associated with increased susceptibility of microbiome. The predominance of Rothia, Prevotella, and Actinomyces may represent progression-associated microbial signatures, warranting mechanistic studies on their pathogenic potential through host-microbe interactions to guide therapeutic targeting.