The impact of tuberculosis and its treatment on the lung and gut microbiota: a global systematic review, meta-analysis, and amplicon-based metagenomic meta-analysis.

BACKGROUND: Tuberculosis (TB) remains the leading cause of bacterial disease-related mortality worldwide. While Koch’s single-agent model has long guided TB diagnostics and treatment, metagenomic studies reveal a resident lung microbiome disrupted by TB and its orally administered therapy, with downstream effects on the gut microbiome. Understanding these disruptions may uncover diagnostic and prognostic indicators. We systematically reviewed 38 studies involving 3394 individuals with TB and healthy controls across four continents to assess the impact of TB and its treatment on lung and gut microbiome diversity, structure, and composition. A meta-analysis of 29 studies and a patient-level amplicon metagenomic meta-analysis (AMMA) of 1617 individuals (1.3 billion reads) were conducted following PRISMA guidelines [PROSPERO: CRD42022329763]. RESULTS: No global consensus exists on TB's impact on lung microbial diversity. Pooled estimates suggest a reduction of ~0.14 in lung diversity and 0.41 in gut diversity. Patient-level analyses showed no overall significant difference in lung diversity (Shannon index), though reductions were evident in China but not South Africa. Conversely, gut diversity tended to be higher in TB cases. Disease status explained only 0.8–9% of variation in lung microbiota and 1.8–9% in gut communities. Composition-wise, TB was associated with depletion of anaerobic core lung genera (e.g. Prevotella, Neisseria, Veillonella, Haemophilus, Fusobacterium, Pseudomonas, Streptococcus, Porphyromonas, Treponema) and gut genera (e.g. Prevotella, Ruminococcus, Faecalibacterium, Clostridium, Roseburia, Rothia, Eubacterium, Escherichia). Treatment further reduced diversity at both sites, with additional loss of core taxa. CONCLUSION: TB is generally linked to reduced lung microbial diversity but increased gut diversity, with effects varying by country, suggesting context-specific rather than universal microbial signatures. Treatment consistently decreases diversity in both lung and gut. Although findings here primarily reflect the upper respiratory tract, they highlight potentially exploitable microbial dynamics. Future studies should integrate additional diversity metrics and broader metadata to refine these insights for advancing their clinical utility. CLINICAL TRIAL: Not applicable.