Mycobacterium tuberculosis, antimicrobials, immunity, and lung–gut microbiota crosstalk: current updates and emerging advances

Abstract

Increasingly, gut microbiota distortions are being implicated in the pathogenesis of several infectious and noninfectious diseases. Specifically, in the absence of an eubiotic microbiota, mice are more prone to colonization and infection by Mycobacterium tuberculosis (Mtb). In this qualitative analysis, the following were observed: (1) antimicrobials cause long-term gut microbiota perturbations; (2) Mtb causes limited and transient disturbances to the lung-gut microbiota; (3) pathogens (e.g., Helicobacter hepaticus) affect microbiota integrity and reduce resistance to Mtb; (4) dysbiosis depletes bacterial species regulating proper immune functioning, reducing resistance to Mtb; (5) dysregulated immune cells fail to express important pathogen-recognition receptors (e.g., macrophageinducible C-type lectin; MINCLE) and Mtb-killing cytokines (e.g., IFN-γ, TNF-α, and IL-17), with hampered phagocytic capability; (6) autophagy is central to the immune system's clearance of Mtb, control of inflammation, and immunity-microbiome balance; (7) microbiota-produced short-chain fatty acids, which are reduced by dysbiosis, affect immune cells and increase Mtb proliferation; (8) commensal species (e.g., Lactobacillus plantarum) and microbiota metabolites (e.g., indole propionic acid) reduce tuberculosis progression; and (9) fecal transplants mostly restored eubiosis, increased immune resistance to Mtb, restricted dissemination of Mtb, and reduced tuberculosis-associated organ pathologies. Overuse of antimicrobials, as shown in mice, is a risk factor for reactivating latent or treated tuberculosis.

Global evolutionary epidemiology, phylogeography and resistome dynamics of Citrobacter species, Enterobacter hormaechei, Klebsiella variicola, and Proteeae clones: A One Health analyses

“…Hence, these opportunistic pathogens demand more attention than they have been given hitherto as the rich resistome repertoire identified in their genomes makes them reservoirs of ARGs 11,14,21,43 . Moreover, being intestinal denizens and commensals, they can easily share these ARGs with facultative and obligate pathogens of humans and animals 22,44–46 . Further, their presence on plants and the environment further suggests that they can share their ARGs with food-borne and water-borne pathogens 44–46 .…”

“…Coupled with plasmid-borne dissemination of ARGs is the selection and expansion of specific drug-resistant clones 11,21 , which quickly spread under antibiotic pressure to overpopulate their environments, facilitating their survival and subsequent spread to other environments 14,22,23 . In cases where such clones harbour resistance plasmids, their expansion almost always lead to the concomitant replication and intra-clonal as well as inter-clonal spread of such plasmids 4,5,7,8,24,25 Thus, as such clones are disseminated through contact, food, water, farms, hospitals, and the environment, they carry with them these resistance plasmids to colonize new hosts and environments 6,26–28 .…”

Culturomics Discloses Anti-Tubercular Enterococci Exclusive of Pulmonary Tuberculosis: A Preliminary Report

“…Previous metagenomics studies all indicated that the repertoire of bacteria in the gut microbiota significantly differed between pulmonary tuberculosis patients and controls, suggesting biological relationships between pulmonary tuberculosis and gut microbiota [ 10 ]. However, contradictory data from these studies complicated the interpretation of these differences.…”

“…In children, microbial richness was not found to significantly differ between TB-positive children and controls, although the Simpson index was found to be significantly lower in TB-positive children [ 30 ] with five different bacterial species found to be significantly balanced between the two groups [ 30 ]. The interpretation of metagenomics studies data was limited by the inherent profounder bias of the method, lack of accurate bacterial species identification [ 10 ], and the fact that detected organisms may not be viable, thus rendering them to be of limited physiological interest.…”

“…However, the factors mention above may not explain all the variations observed in the clinical spectrum of tuberculosis and the hypothesis that individual microbiota may also govern part of the clinical expression of tuberculosis, has emerged [ 10 ]. A few studies recently indicated significant correlations between the repertoire of microorganisms in the digestive tract microbiota and pulmonary tuberculosis [ 11 , 12 , 13 ], yet these studies relied upon metagenomics, leaving it unknown whether living organisms were indeed significantly associated with tuberculosis.…”