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.
Highlights
IntroductionAbout 5–10% of subjects with primary M. tuberculosis infection may immediately manifest active TB (primary TB), defined as clinical symptoms of disease, microbiological confirmation of M. tuberculosis, or both, or undergo clinical reactivation of the latent tuberculosis infection (LTBI) throughout life (secondary TB), because of failure to develop or maintain an effective immune response
We address the current understanding of the host immune response against M. tuberculosis infection, the emerging evidence on the possible role of gut and lung microbiota in TB pathogenesis, and the available data on the possible use of probiotics in combination with standard antibiotic therapy for the treatment of TB
M. tuberculosis infection and progression to active TB is modified by intestinal coinfection with Helicobacter species; (3) the anaerobes present in the lung coming from the oral cavity by aspiration produce metabolites that can reduce lung immunity and predict the progression of infection to active disease; (4) the increased susceptibility to reinfection of patients who have been previously treated for TB is possibly related to the depletion of antigenic epitopes for T cells in the intestinal commensal microbial flora; and (5) the prolonged antibiotic treatment used for TB has a long-lasting impact on the composition of gut microbiota [68]
Summary
About 5–10% of subjects with primary M. tuberculosis infection may immediately manifest active TB (primary TB), defined as clinical symptoms of disease, microbiological confirmation of M. tuberculosis, or both, or undergo clinical reactivation of the LTBI throughout life (secondary TB), because of failure to develop or maintain an effective immune response. Immune deficiencies, malnutrition, and bacterial load are the most important factors for the rapid replication of M. tuberculosis and progression to active TB [2]. Accumulating evidence suggests that the human microbiota dysbiosis could modulate susceptibility to M. tuberculosis infection, progression from LTBI to active TB, and response to antituberculosis therapy [5]. We address the current understanding of the host immune response against M. tuberculosis infection, the emerging evidence on the possible role of gut and lung microbiota in TB pathogenesis, and the available data on the possible use of probiotics in combination with standard antibiotic therapy for the treatment of TB
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