The Human Microbiome in the Fight Against Tuberculosis

Abstract

The human microbiome is an intriguing potentially modifiable risk factor in our arsenal against , the leading infectious disease killer globally. Previous studies have shown associations between the human microbiome and pulmonary disease states; however, etiological links between the microbiome and tuberculosis (TB) infection or disease remain unclear. Immunomodulatory roles of the microbiome may prove to be a critical asset in the host response against TB, including in preventing TB infection, reducing progression from latency, mitigating disease severity, and lowering the incidence of drug resistance and coinfections. This review examined the associations between TB and the gut and lung microbiome. Eight studies were identified through a PubMed database search, including one animal study ( = 1), case report ( = 1), and case-control studies ( = 6). TB infection and disease were associated with reduced gastrointestinal microbial diversity in a murine model and human case report. Sputum microbial diversity differed by TB status in case-control studies, although some reported heterogeneous findings. Current evidence suggests that the gut and lung microbiome are associated with TB infection and disease. However, as studies are limited, etiological and longitudinal research is needed to determine clinical relevance.

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

“…Although a direct effect of the microbiome on dormancy in Mtb has not been described, it is not impossible as the microbiome is known to increase macrophage killing and ROS and NO production through NOD1 and TLR signaling. 8,19 Thus, the ability of NO and ROS to cause dormancy through DosR (DevR) activation in Mtb should stimulate further research into this possibility of the microbiome influencing activation of Mtb dormancy. 38,76 Furthermore, the ability of nutrient starvation and hypoxia to cause dormancy reduces autophagy and ROS as these two processes are triggered by or cause nutrient starvation, respectively.…”

“…These signals induce macrophages and den-dritic cells (DCs) to phagocytose the bacilli, produce cathelicidin (an antimicrobial peptide (AMP)), and destroy Mtb through autophagy. 19 TLR and NOD activate certain autophagy genes (atg) to form double-membraned autophagosomes around pathogens. These autophagosomes are then labeled with microtubule-associated protein 1 light chain 3 alpha (LC3) and fused with lysosomes to form single-membraned autolysosomes for degradation.…”

Prevalence and clinical significance of respiratory viruses and bacteria detected in tuberculosis patients compared to household contact controls in Tanzania: a cohort study

“…The differences in airway microorganism populations could indicate that respiratory pathogens can be involved in TB pathogenesis [11]. However, little is known about the prevalence of respiratory pathogens, whether viral or bacterial, and their role in clinical presentation in TB.…”

Gut microbes as future therapeutics in treating inflammatory and infectious diseases: Lessons from recent findings

“…the emergence of resistant strains and the lack of personalized treatment, the gut microbiotabased treatment is now considered as an effective approach. Considering the regulatory role of the gut microbiota on host immunity for maintaining the pulmonary physiology (lung-gut axis), prompted the use of the gut microbes and/or probiotics-based therapy for treating tuberculosis (TB) [208]. Gut microbes confer protection to TB by enhancing the synthesis of the antimicrobial components by Prevotella and Veillonella in the lungs and by inducing the pro-inflammatory response in the pulmonary lymphocytes [209].…”