TB and treatment reshape the lung and gut microbiome

Tuberculosis (TB) is still the leading cause of bacterial disease deaths worldwide. For more than a century scientists worked from Koch’s single-causative-agent model, focusing on finding and treating a single pathogen. More recently, researchers have discovered that the lungs host a complex microbiome and that this community can be disrupted by TB disease and by the drugs used to treat it; those changes can ripple through and affect the gut microbiome as well. To make sense of many scattered studies, Adrian Muwonge and colleagues carried out a global systematic review and meta-analysis. They compiled 38 studies including 3,394 people with TB and healthy controls, and they followed PRISMA guidelines and a pre-registered PROSPERO protocol (CRD42022329763). They also combined data at the patient level in an amplicon-based metagenomic meta-analysis to look for consistent patterns. The goal was to measure how TB and TB treatment change microbial diversity, community structure, and which bacterial groups become more or less common in the lung and gut.

The team used multiple approaches to quantify effects. A formal meta-analysis of 24 studies estimated an overall reduction in lung and gut diversity of 0.14–0.41. The patient-level amplicon metagenomic meta-analysis included 1,617 individuals and 1.3 billion reads to validate those associations. Diversity measured by the Shannon index showed no consistent overall lung difference across all patients, but subgroup analysis found reduced lung diversity in China and not in South Africa. In the gut, TB was associated with higher diversity in most countries. Disease status explained only a small share of microbiome variation — about 0.8–9% for lung and 1.8–9% for gut. Across studies, TB was linked to depletion in the lung of Prevotella, Neisseria, Veillonella, Haemophilus, Fusobacterium, Pseudomonas, Streptococcus, Porphyromonas, and Treponema, and depletion in the gut of Prevotella, Ruminococcus, Faecalibacterium, Clostridium, Roseburia, Rothia, Eubacterium, and Escherichia. TB treatment was consistently associated with reduced diversity in both lung and gut and loss of key core genera.

These findings point to a complex picture: TB disease generally correlates with reduced microbial diversity in the lung but not consistently in the gut, while the drugs used to treat TB more reliably reduce diversity in both sites. The small share of variation explained by disease status means the microbiome alone is unlikely to be a standalone diagnostic; the diagnostic value of microbiome signatures remains uncertain. Still, the repeated depletion of core genera in both lung and gut suggests a disrupted gut–lung axis that could be relevant for prognosis or supportive therapies. By mapping which bacterial groups are lost during disease and treatment, researchers can begin to explore whether microbiome-based markers, adjunctive microbiome therapies, or timing of interventions might improve TB control. The study emphasizes the need for more standardized, geographically diverse work to translate these microbial patterns into clinical tools.