Chronic obstructive pulmonary disease (COPD) is the third commonest cause of death globally, and manifests as a progressive inflammatory lung disease with no curative treatment. The lung microbiome contributes to COPD progression, but the function of the gut microbiome remains unclear. Here we examine the faecal microbiome and metabolome of COPD patients and healthy controls, finding 146 bacterial species differing between the two groups. Several species, includingStreptococcus sp000187445,Streptococcus vestibularisand multiple members of the familyLachnospiraceae, also correlate with reduced lung function. Untargeted metabolomics identifies a COPD signature comprising 46% lipid, 20% xenobiotic and 20% amino acid related metabolites. Furthermore, we describe a disease-associated network connectingStreptococcus parasanguinis_Bwith COPD-associated metabolites, including N-acetylglutamate and its analogue N-carbamoylglutamate. While correlative, our results suggest that the faecal microbiome and metabolome of COPD patients are distinct from those of healthy individuals, and may thus aid in the search for biomarkers for COPD.

The composition of the lung microbiome is increasingly well characterised, with changes in microbial diversity or abundance observed in association with several chronic respiratory diseases such as asthma, cystic fibrosis, bronchiectasis, and chronic obstructive pulmonary disease. However, the precise effects of the microbiome on pulmonary health and the functional mechanisms by which it regulates host immunity are only now beginning to be elucidated. Bacteria, viruses, and fungi from both the upper and lower respiratory tract produce structural ligands and metabolites that interact with the host and alter the development and progression of chronic respiratory diseases. Here, we review recent advances in our understanding of the composition of the lung microbiome, including the virome and mycobiome, the mechanisms by which these microbes interact with host immunity, and their functional effects on the pathogenesis, exacerbations, and comorbidities of chronic respiratory diseases. We also describe the present understanding of how respiratory microbiota can influence the efficacy of common therapies for chronic respiratory disease, and the potential of manipulation of the microbiome as a therapeutic strategy. Finally, we highlight some of the limitations in the field and propose how these could be addressed in future research.

Chronic respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF), are among the leading causes of mortality and morbidity worldwide. In the past decade, the interest in the role of microbiome in maintaining lung health and in respiratory diseases has grown exponentially. The advent of sophisticated multiomics techniques has enabled the identification and characterisation of microbiota and their roles in respiratory health and disease. Furthermore, associations between the microbiome of the lung and gut, as well as the immune cells and mediators that may link these two mucosal sites, appear to be important in the pathogenesis of lung conditions. Here we review the recent evidence of the role of normal gastrointestinal and respiratory microbiome in health and how dysbiosis affects chronic pulmonary diseases. The potential implications of host and environmental factors such as age, gender, diet and use of antibiotics on the composition and overall functionality of microbiome are also discussed. We summarise how microbiota may mediate the dynamic process of immune development and/or regulation focusing on recent data from both clinical human studies and translational animal studies. This furthers the understanding of the pathogenesis of chronic pulmonary diseases and may yield novel avenues for the utilisation of microbiota as potential therapeutic interventions.

Workers in the mining and construction industries are at increased risk of respiratory and other diseases as a result of being exposed to harmful levels of airborne particulate matter (PM) for extended periods of time. While clear links have been established between PM exposure and the development of occupational lung disease, the mechanisms are still poorly understood. A greater understanding of how exposures to different levels and types of PM encountered in mining and construction workplaces affect pathophysiological processes in the airways and lungs and result in different forms of occupational lung disease is urgently required. Such information is needed to inform safe exposure limits and monitoring guidelines for different types of PM and development of biomarkers for earlier disease diagnosis. Suspended particles with a 50% cut-off aerodynamic diameter of 10 µm and 2.5 µm are considered biologically active owing to their ability to bypass the upper respiratory tract's defences and penetrate deep into the lung parenchyma, where they induce potentially irreversible damage, impair lung function and reduce the quality of life. Here we review the current understanding of occupational respiratory diseases, including coal worker pneumoconiosis and silicosis, and how PM exposure may affect pathophysiological responses in the airways and lungs. We also highlight the use of experimental models for better understanding these mechanisms of pathogenesis. We outline the urgency for revised dust control strategies, and the need for evidence-based identification of safe level exposures using clinical and experimental studies to better protect workers’ health.

Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis , is the leading cause of mortality worldwide due to a single infectious agent. The pathogen spreads primarily via aerosols and especially infects the alveolar macrophages in the lungs. The lung has evolved various biological mechanisms, including oxidative stress (OS) responses, to counteract TB infection. M. tuberculosis infection triggers the generation of reactive oxygen species by host phagocytic cells (primarily macrophages). The development of resistance to commonly prescribed antibiotics poses a challenge to treat TB; this commonly manifests as multidrug resistant tuberculosis (MDR‐TB). OS and antioxidant defense mechanisms play key roles during TB infection and treatment. For instance, several established first‐/second‐line antitubercle antibiotics are administered in an inactive form and subsequently transformed into their active form by components of the OS responses of both host (nitric oxide, S ‐oxidation) and pathogen (catalase/peroxidase enzyme, EthA). Additionally, M. tuberculosis has developed mechanisms to survive high OS burden in the host, including the increased bacterial NADH/NAD ⁺ ratio and enhanced intracellular survival (Eis) protein, peroxiredoxin, superoxide dismutases, and catalases. Here, we review the interplay between lung OS and its effects on both activation of antitubercle antibiotics and the strategies employed by M. tuberculosis that are essential for survival of both drug‐susceptible and drug‐resistant bacterial subtypes. We then outline potential new therapies that are based on combining standard antitubercular antibiotics with adjuvant agents that could limit the ability of M. tuberculosis to counter the host’s OS response.

Gut microbiota is established during birth and evolves with age, mostly maintaining the commensal relationship with the host. A growing body of clinical evidence suggests an intricate relationship between the gut microbiota and the immune system. With ageing, the gut microbiota develops significant imbalances in the major phyla such as the anaerobic Firmicutes and Bacteroidetes as well as a diverse range of facultative organisms, resulting in impaired immune responses. Antimicrobial therapy is commonly used for the treatment of infections; however, this may also result in the loss of normal gut flora. Advanced age, antibiotic use, underlying diseases, infections, hormonal differences, circadian rhythm, and malnutrition, either alone or in combination, contribute to the problem. This nonbeneficial gastrointestinal modulation may be reversed by judicious and controlled use of antibiotics and the appropriate use of prebiotics and probiotics. In certain persistent, recurrent settings, the option of faecal microbiota transplantation can be explored. The aim of the current review is to focus on the establishment and alteration of gut microbiota, with ageing. The review also discusses the potential role of gut microbiota in regulating the immune system, together with its function in healthy and diseased state.