The Gut Microbiome as a Biomarker for Tuberculosis Recurrence and Treatment Resistance: Addressing Gaps in Prognostic Tools

Gut microbiome as a biomarker for tuberculosis treatment

Abstract

Tuberculosis (TB) persists as a formidable global health challenge, characterized by high rates of post-treatment recurrence, relapse, and the emergence of multidrug-resistant (MDR) strains, which remain inadequately predicted by conventional sputum-based, radiographic, and immunological biomarkers. Emerging evidence underscores the gut microbiome as a pivotal, yet underexploited, modulator of TB therapeutic outcomes, wherein Mycobacterium tuberculosis (MTB) infection and protracted antimicrobial regimens induce enduring intestinal dysbiosis. This perturbation alters systemic immunity, modulates xenobiotic metabolism, and compromises host resilience against reinfection. Insights from prospective human cohorts in high-burden settings, complemented by murine, non-human primate, and gnotobiotic models, consistently implicate depleted short-chain fatty acid (SCFA)-producing taxa (e.g., Ruminococcaceae, Lachnospiraceae) and enriched pathobionts (e.g., Proteobacteria, Fusobacterium) in the progression from latency to active disease, therapeutic failure, and recurrent TB. Multi-omics integrations, encompassing metagenomics, metabolomics, and host transcriptomics, reveal that composite microbial-metabolite signatures outperform single-taxon analyses in prognosticating relapse and resistance, though validation across heterogeneous populations and clinical workflows is nascent. Machine learning algorithms and network analyses applied to these datasets herald the development of microbiome-derived risk indices and poly-marker panels, albeit constrained by inconsistencies in sampling, bioinformatics pipelines, and endpoint definitions. Critically, the gut microbiome emerges not only as a non-invasive prognostic reservoir but also as a tractable therapeutic locus, with interventions such as probiotics, prebiotics, fecal microbiota transplantation (FMT), and precision microbiota engineering poised to augment TB risk stratification, mitigate recurrence, and curb antimicrobial resistance dissemination.