Exploring Differences in Alveolar Microbiome Between Pulmonary Tuberculosis Patients with Different Treatment Outcomes: A Metagenomic Study from China

This study aimed to investigate differences in the composition and functional characteristics of alveolar microbiota in patients with pulmonary tuberculosis (PTB) exhibiting differential therapeutic responses. Thirty-two patients with drug-sensitive PTB who had completed standard anti-tuberculosis therapy were enrolled and classified into good-response (n = 16) and poor-response (n = 16) groups. Bronchoalveolar lavage fluid (BALF) samples were collected and analysed using metagenomic sequencing to characterize microbial community and functional pathways. No significant differences were observed in α-diversity between the two groups; however, β-diversity analysis demonstrated marked differences in microbial community structure (ANOSIM, R = 0.381, P < 0.001). The good efficacy group was characterized by enrichment of Prevotella, Staphylococcus, and oral commensal bacteria including Fusobacterium and Rothia, together with significantly increased pathways related to peptidoglycan biosynthesis, glutathione metabolism, energy production, and DNA repair. In contrast, the poor efficacy groups was characterised by enrichment of Microbacterium and activation of functional pathways associated with biofilm formation, urea cycle–mediated ammonia production, and apoptosis. These findings suggest that both the taxonomic composition and functional activity of the pulmonary microbiome are closely associated with anti-tuberculosis treatment outcomes. Microbial communities in patients with favourable responses may support recovery through immune modulation, antioxidative capacity, and metabolic competition, whereas microbiota enriched in poor responders may contribute to treatment failure via biofilm formation and production of immunosuppressive metabolites such as ammonia.