Microbiome-immune interactions in tuberculosis

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.

Differential Diagnosis of Latent Tuberculosis Infection and Active Tuberculosis: A Key to a Successful Tuberculosis Control Strategy

“…However, the impact of microbiota on host defense against M. tuberculosis infection is poorly understood. A recent review published in PLOS Pathogens summarized 14 microbiome studies performed on animal models of TB and patients with TB (Mori et al, 2021). Among these studies, nine focused on the relationship between microbiota in the intestinal tract and M. tuberculosis, including five studies on patients with TB, three studies on mouse models, and one study on rhesus macaques.…”

Exploring the role of Microbiome in Susceptibility, Treatment Response and Outcome among Tuberculosis Patients from Pakistan: study protocol for a prospective cohort study (Micro-STOP)

“…Although, a number of factors that modulate the risk of progression from one stage of the disease to another has been documented, the underlying biological modulators of the risk remains elusive especially with regard to the microbiome 10. Emerging evidence suggests that the microbiome is likely to play a critical role in TB pathogenesis as well as in treatment response and outcome, primarily due to multifaceted interactions between the pathogen, microbiome and host immune response 4 11…”

Novel In Silico Insights into Rv1417 and Rv2617c as Potential Protein Targets: The Importance of the Medium on the Structural Interactions with Exported Repetitive Protein (Erp) of Mycobacterium tuberculosis

“…TB is a chronic disease caused by the intracellular pathogen Mycobacterium tuberculosis (Mtb) [5,8,9]. Despite being a preventable and curable disease, TB is associated with high rates of morbidity and mortality [9,10].…”

“…TB is a chronic disease caused by the intracellular pathogen Mycobacterium tuberculosis (Mtb) [5,8,9]. Despite being a preventable and curable disease, TB is associated with high rates of morbidity and mortality [9,10]. The ignorance of the immune response in the progression from the latent to the active form in TB, in addition to the different mechanisms of the bacteria to survive in hostile conditions, has resulted in an increase in deaths in recent years [6,11].…”