The Role of Gut and Lung Microbiota in Susceptibility to Tuberculosis

Abstract

Tuberculosis is one of the most common infectious diseases and infectious causes of death worldwide. Over the last decades, significant research effort has been directed towards defining the understanding of the pathogenesis of tuberculosis to improve diagnosis and therapeutic options. Emerging scientific evidence indicates a possible role of the human microbiota in the pathophysiology of tuberculosis, response to therapy, clinical outcomes, and post-treatment outcomes. Although human studies on the role of the microbiota in tuberculosis are limited, published data in recent years, both from experimental and clinical studies, suggest that a better understanding of the gut-lung microbiome axis and microbiome-immune crosstalk could shed light on the specific pathogenetic mechanisms of Mycobacterium tuberculosis infection and identify new therapeutic targets. In this review, we address the current knowledge of the host immune responses against Mycobacterium tuberculosis infection, the emerging evidence on how gut and lung microbiota can modulate susceptibility to tuberculosis, the available studies on the possible use of probiotic-antibiotic combination therapy for the treatment of tuberculosis, and the knowledge gaps and future research priorities in this field.

Keywords: Mycobacterium tuberculosis; children; gut; infection; lung; microbiome; microbiota; tuberculosis.

Figure 1

Environmental alterations such as diet, the use of broad-spectrum antibiotics, and colonization by pathogenic bacteria can alter the normal composition of the intestinal microbiota. M. tuberculosis, through mostly unknown mechanisms, is also able to modulate the diversity of the intestinal flora. The response of upper pathway epithelial cells and resident invariant T lymphocytes (MAITs) is modulated by the gut microbiota. These can assist the macrophage response to infection. The intestinal microbiota is a strong modulator of the T helper response in the lung and, as such, could affect the ability of macrophages to eliminate M. tuberculosis through the increase in the production of IFN-γ, IL-12, and reactive oxygen species. Bacterial-derived metabolites and other mediators are among those responsible for maintaining the dynamic balance between the intestinal and lung microbiota.

Figure 2

Hypothesized role of the lung microbiota in the pathogenesis of tuberculosis.