Metagenomic insights into the pulmonary microbiome of drug-sensitive and multidrug-resistant tuberculosis patients

Background While the pulmonary microbiota may influence TB pathogenesis, direct comparisons between drug-sensitive (DS-TB) and multidrug-resistant (MDR-TB) patients remain scarce. This study explored microbiome differences between these groups.Methods Bronchoalveolar lavage fluid (BALF) from 30 prospective patients (11 DS-TB, 19 MDR-TB) was analysed via metagenomic sequencing.Results Patients with MDR-TB showed lower α-diversity and distinct β-diversity compared with patients with DS-TB. Streptococcus and Prevotella were relatively enriched in DS-TB, whereas Staphylococcus, Cutibacterium, and Mycobacterium were more abundant in MDR-TB. DS-TB showed enrichment of 45 carbohydrate-active enzyme families and core metabolic annotations, whereas MDR-TB showed enrichment of infection- and immunity-related functional annotations and a less connected taxonomic network. An exploratory random forest analysis identified six candidate genera and yielded an internally cross-validated AUC of 0.957.Conclusions MDR-TB was associated with lower pulmonary microbial diversity, altered community composition, and shifts in predicted microbial functions. These findings characterise lower-airway microbiome differences between DS-TB and MDR-TB and provide a basis for further validation.