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.

Investigating potential transmission of antimicrobial resistance in an open-plan hospital ward: a cross-sectional metagenomic study of resistome dispersion in a lower middle-income setting

“…The relationship between TB and carriage of OXA-1, catB3, rmtB and dfrA14 is likely to reflect the impact of gut microbiota disruption arising as a result of prolonged hospital stay and antibiotic therapy. A previous study has reported the relative abundance of gut Firmicutes to be decreased in those with TB, and the prevalence of Proteobacteria to be increased [27]. We observed a reduction in Firmicutes and an increase in Escherichia-Shigella, with the latter correlated with OXA-1, dfrA14 and catB3.…”

Profound remission in Crohn’s disease requiring no further treatment for 3–23 years: a case series

“…We hypothesize that there is a complex interplay, where a predisposition, stemming from innate immune deficiencies (given this particularly is involved in intracellular bacterial infections and perhaps evolved alongside the resident gut flora), that likely arise from certain deficiencies of the gut microbiome. This has been shown to be the case in tuberculosis susceptibility [32]. Genetic factors, such as the NOD2CARD15 mutations contributes to risk of developing disease, as these enable the pathogenesis of CD and also have been shown to confer an increased risk to mycobacterial infections [33,34].…”

Microbiome-immune interactions in tuberculosis

“…Here, we focus on the emerging concepts of direct and indirect contributions of the host microbiome to host defense mechanisms against M . tuberculosis infection [ 44 ].…”

“…With the growing understanding of how dynamic interactions between microbiota and the host immune system define the development and functions of lymphocytes [ 157 ], there is a growing interest in how the microbiota shapes adaptive immune responses that are critical for the host control of M . tuberculosis infection [ 44 , 158 ].…”

“…Characterization of the microbiome composition of TB patients and the M. tuberculosisinfected host in animal models has been the subject of significant efforts (Table 1) and has been reviewed in significant detail elsewhere [8,[41][42][43][44]. Table 1 and Fig 1A and 1B summarize the findings from colonic (fecal) and lung microbiota of humans and animal models of M. tuberculosis infection compared to noninfected "controls".…”