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

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-host-interactions 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.