Abstract
Tuberculosis (TB) remains an infectious disease of global significance and a leading cause of death in low- and middle-income countries. Significant effort has been directed towards understanding Mycobacterium tuberculosis genomics, virulence, and pathophysiology within the framework of Koch postulates. More recently, the advent of “-omics” approaches has broadened our appreciation of how “commensal” microbes have coevolved with their host and have a central role in shaping health and susceptibility to disease. It is now clear that there is a diverse repertoire of interactions between the microbiota and host immune responses that can either sustain or disrupt homeostasis. In the context of the global efforts to combatting TB, such findings and knowledge have raised important questions: Does microbiome composition indicate or determine susceptibility or resistance to M. tuberculosis infection? Is the development of active disease or latent infection upon M. tuberculosis exposure influenced by the microbiome? Does microbiome composition influence TB therapy outcome and risk of reinfection with M. tuberculosis? Can the microbiome be actively managed to reduce risk of M. tuberculosis infection or recurrence of TB? Here, we explore these questions with a particular focus on microbiome-immune interactions that may affect TB susceptibility, manifestation and progression, the long-term implications of anti-TB therapy, as well as the potential of the host microbiome as target for clinical manipulation.
Highlights
Tuberculosis (TB) remains an infectious disease of global significance and a leading cause of death in low- and middle-income countries
Structural components in particular the Gram-negative bacterial cell wall component lipopolysaccharide (LPS) can trigger substantial pro-inflammatory responses at local and distant sites if epithelial barrier functions are perturbed. These findings indicate that M. tuberculosis infection is associated with a gut “dysbiosis.” While the cause-and-effect relationship between TB and gut dysbiosis is currently unknown, longitudinal analysis of the fecal microbiota in a mouse model suggest that M. tuberculosis infection causes a significant decrease of the relative abundances of the Lachnospiraceae and Ruminococcaceae families within days of infection [53]
Given that mycobacterial DNA was not detected in fecal samples of infected mice, the selective decrease in bacterial diversity and the dysbiosis observed was unlikely due to the presence of M. tuberculosis within the gut. These findings suggest that the dysbiosis of the colonic microbiota associated with TB may reflect early alterations in the mucosal immune milieu presented in the gut as a consequence of M. tuberculosis infection in the lung, and their translation to selective pressures on the colonic microbiota [53]
Summary
The colonization of the host by microorganisms begins within minutes of birth or hatching. The expansion of cultured microbes from different body sites using techniques in anaerobic microbiology helped explain and expand the appreciation of the mutualistic relationships between these communities and their host in terms of structural, metabolic, and immune development [24]. It is important to note that increased and decreased relative abundance, as well as no significant changes have been reported (Table 1 and Fig 1A), highlighting the challenges posed by integrating data obtained across different host organisms, control populations, and study designs. These 2 bacterial families of the phylum Firmicutes represent the 2 numerically most abundant groups of Gram-positive bacteria in the human colon [47]. Members of both groups are recognized for their capacity to utilize carbohydrates in simple and polymeric forms and govern the schemes of anaerobic fermentation that produce the short-
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