Gut microbiome dysbiosis and associated metabolome changes in tuberculosis patients resolve partially post-therapy

Abstract Background Mycobacterium tuberculosis (Mtb) infection in the host and subsequent treatment with anti-tuberculosis drugs impact lung pathophysiology and influence the lung and gut microbiome. Elucidating the role of the gut microbiome and its metabolites in the perturbed metabolic and immune functions observed in tuberculosis (TB) might help design corrective prebiotic and probiotic mixtures. Methodology In this study, fecal samples ( n = 107) of drug-naïve active TB patients (ATB) and controls (other respiratory disease: NTB and healthy) from the two clinical sites were analyzed for microbiota composition (16S rRNA sequencing), metabolites (GC-TOF-MS), and their correlation. In addition, a longitudinal follow-up study was conducted to understand the dynamics of the microbiota and metabolites during anti-TB treatment in a small cohort ( n = 10). Results Gut microbiota showed site-specificity; however, an overall reduction in alpha diversity was observed in disease states compared with healthy subjects. Underrepresentation of gut commensals ( Faecalibacterium , Ligilactobacillus and Romboustia ) and overrepresentation of Thomasclavelia and Clostridioides were observed among active TB patients. The longitudinally followed-up ATB subjects undergoing treatment showed a time-dependent increase in beta-diversity variance. Over time, the beta diversity of follow-up subjects was almost similar to that of healthy controls. Decrease in the abundance of Streptococcus occurred after anti-TB treatment, with higher levels of opportunistic pathogens, such as Escherichia and Stenotrophomonas . Similarly, specific fecal metabolites also returned to pretreatment levels in relative abundance at later time points. Conclusions The gut microbiota of TB patients showed dysbiosis at the time of case presentation and partially resolved upon complete therapeutic interventions. Partial recovery of microbiota observed during treatment is also reflected in the fecal metabolome, indicating the possible use of microbiome and metabolites as adjunct therapeutics in TB.