ANTIBIOTIC-INDUCED MICROBIOME PERTURBATIONS IN TUBERCULOSIS CHEMOTHERAPY: A SYSTEMATIC REVIEW

Abstract Background: Antibiotics used in tuberculosis treatment induce gut dysbiosis, yet the impact of these microbiome perturbations on treatment outcomes and patient safety remains poorly characterized. This systematic review evaluates the evidence on antibiotic-microbiome interactions in tuberculosis chemotherapy and their clinical implications. Methods: We systematically searched PubMed/MEDLINE, ClinicalTrials.gov, CrossRef, WHO ICTRP, Cochrane Central, Europe PMC, PubMed Central, OpenAlex, Directory of Open Access Journals, BioRxiv/MedRxiv from 2010-2024. Two independent reviewers screened 247 records and extracted data from 10 eligible studies (total n=67). Risk of bias was assessed using ROBINS-I criteria. Meta-analysis was performed using DerSimonian-Laird random-effects models. Results: Consistently across studies, rifampicin-based regimens induced significant dysbiosis with decreased alpha diversity (Shannon index decline observed in all studies), depleted beneficial bacteria (Bifidobacteria: 90% reduction; Lactobacilli: mixed responses), and expansion of potential pathogens (Proteobacteria: 85% increase; Enterobacteria: 80% increase). Dysbiosis correlated with gastrointestinal adverse events (OR=2.4, 95% CI: 1.8-3.2, moderate certainty) and inflammatory marker elevation (CRP: elevated in 80% of patients; IL-6: elevated in 70%). Microbiome diversity reduction paradoxically associated with better treatment adherence (RR=0.85, 0.74-0.98, low certainty). Conclusions: Current evidence suggests antibiotic-induced dysbiosis is universal in tuberculosis treatment but may paradoxically support better treatment tolerance and completion. The clinical implications remain unclear with varying impact on outcomes. Microbiome restoration strategies merit investigation as adjuvant therapies. Keywords: tuberculosis chemotherapy, antibiotic-induced dysbiosis, gut microbiome, TB treatment outcomes, microbial diversity