The gut microbiome in tuberculosis susceptibility and treatment response: guilty or not guilty?

Abstract

Although tuberculosis (TB) is a curable disease, it remains the foremost cause of death from a single pathogen. Globally, approximately 1.6 million people died of TB in 2017. Many predisposing factors related to host immunity, genetics and the environment have been linked to TB. However, recent evidence suggests a relationship between dysbiosis in the gut microbiome and TB disease development. The underlying mechanism(s) whereby dysbiosis in the gut microbiota may impact the different stages in TB disease progression, are, however, not fully explained. In the wake of recently emerging literature, the gut microbiome could represent a potential modifiable host factor to improve TB immunity and treatment response. Herein, we summarize early data detailing (1) possible association between gut microbiome dysbiosis and TB (2) the potential for the use of microbiota biosignatures to discriminate active TB disease from healthy individuals (3) the adverse effect of protracted anti-TB antibiotics treatment on gut microbiota balance, and possible link to increased susceptibility to Mycobacterium tuberculosis re-infection or TB recrudescence following successful cure. We also discuss immune pathways whereby the gut microbiome could impact TB disease and serve as target for clinical manipulation.

Keywords: Gut commensal; Immune response; Microbial imbalance; Microbiome biosignatures; Mycobacterium tuberculosis; Tuberculosis therapy.

Fig. 1

Model for gut microbiome and metabolite regulation of cytokine responses during tuberculosis disease. Heterogeneity and balance in gut microbiota and metabolites provide different signals that educate the immune system. Exposure to M.tb infection triggers gut–lung homing of pro- and anti-inflammatory T lymphocytes. Homeostatic cytokine lung environment is maintained. Macrophages clear infection or contain pathogen within granulomas in people shown as No TB disease. By contrast, factors such as antibiotics use, HIV infection and diabetes alter microbiota balance leading to defective/skewed T lymphocytes activation. M.tb infectious challenge in this state triggers over-abundance of a T lymphocyte subsets upon gut–lung homing. Macrophage response is impaired. Defective T and B cell cooperation results in poor control of infection, promotes infection of adjacent lung tissues and progression to active TB disease