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.

Fig 1

Alterations in microbiome composition (A = gut; B = respiratory tract) in individuals with active TB compared to controls. Significantly over- and underrepresented bacteria in the gut (A) and lungs (B) of TB patients (circle), mice (rhombus), or macaques (triangle) models of TB. Taxonomic details are shown, and over- or underrepresentation of the taxonomic level reported by each study is indicated by a red or blue shape, respectively.

Fig 2

Alterations in microbiome composition (A = gut; B = respiratory tract) of patients upon TB antibiotics treatment. Significantly over- and underrepresented bacteria in the gut (A) and lungs (B) of TB patients (circle), mice (rhombus), or macaques (triangle) models of TB undergoing therapy for drug-sensitive or multidrug-resistant TB. Taxonomic details are shown, and over- or underrepresentation of the taxonomic level reported by each study is indicated by a red or blue shape, respectively.

Fig 3. Proposed microbiome-immune interactions in M. tuberculosis infection.

Microbiota of the upper and lower respiratory tract may define epithelial barrier integrity, M cell frequency, antimicrobial defense, composition, and functionality of innate and adaptive immune mechanisms. Through the gut-lung axis, the microbiota of the intestinal tract influences barrier and immune functions in the periphery and at sites of M. tuberculosis infection. Fig 3 was created with BioRender.