The microbiome and gut–lung axis in nontuberculous mycobacterial pulmonary disease

Abstract

Nontuberculous mycobacterial pulmonary disease (NTM-PD) is increasingly recognised as a significant global health concern. It is characterised by a highly heterogenous clinical course and remains poorly understood, from host susceptibility to disease pathophysiology, and is notoriously difficult to treat. Recent advances highlight the microbiome as a critical modulator of host physiology, with site-specific ‘microbiota’ influencing the delicate balance between health, infection and disease. While microbial populations vary across discrete anatomical sites, there is a growing recognition that they are interconnected. For example, gut microbes can influence immune cell functions in the lung via the gut–lung axis (GLA). Drawing parallels with other related chronic respiratory diseases, it is hypothesised that microbiota–hostinteractions shape susceptibility and manifestation of NTM-PD. This review synthesises current knowledge of some key host susceptibility factors in NTM-PD, and their potential interactions with host microbiota. With only recently emerging studies, we explore the potential role of the GLA in NTM-PD, given its promising links to microbial communities and immunological and metabolic pathways. We assess the limited, but growing body of research on the lung microbiota in NTM-PD and evaluate the small number of studies on faecal microbiota in NTM-PD. By considering insights across anatomical sites, this review aims to contextualise the microbiome within multiple dimensions of NTM-PD, including host susceptibility, disease progression, treatment responsiveness, and the effects of antibiotic therapy. A better understanding of the microbiome in NTM-PD could hold promise in uncovering the complex and multifactorial mechanisms that contribute to the heterogenous clinical course and challenging management of NTM-PD.