Microbiome effects on immunity, health and disease in the lung

Abstract

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.

Figure 1

Factors affecting microbiome in early life and adulthood. Host microbiome in both early and adult life is affected by various factors. Preterm (during gestation) determinants of microbiome include maternal BMI and pharmacotherapy, whereas post-term factors such as mode of delivery, duration of breastfeeding, day-care attendance and diet (throughout life) significantly influence the microbiota composition. Environmental factors, for example, exposure to cigarette smoke/air pollution/allergens, respiratory infections as well as host-associated factors such as age, gender, BMI and onset of chronic diseases could result in ‘dysbiosis'.

Figure 2

Roles of commensal bacteria and/or their components/metabolites in regulation of host immunity. Commensal bacteria induce the lysozyme production by Paneth cells that reduces the colonisation of pathogenic bacteria via NOD2 sensing. Moreover, these beneficial bacteria ferment dietary fibres to produce SCFAs, which then promotes the secretion of anti-inflammatory cytokines (IL-10, IL-21) by immune cells. Murein lipoprotein (MLP), a Gram-negative commensal bacterial cell wall component, can induce production of IgG, which primes macrophages and dendritic cells to remove antigens/pathogens. B. fragilis selectively polarises macrophages into proinflammatory M1 phenotype leading to enhanced pathogen clearance/inflammation.

Figure 3

Interaction matrix: risk factors for chronic respiratory diseases and associated pathology with microbiome. Major risk factors could lead to immune dysregulation, characteristic pathology and ‘dysbiosis'. Altered microbiome could then aggravate the host immunity and disease pathology. Notably, aberrant immune response could further skew the microbiome favoring specific pathogens typically reported in respiratory diseases, such as COPD and CF. LF, lung function.