Microbial dysbiosis and asthma
Nasal, lung and gut microbiota play several important roles in the development, regulation, and maintenance of healthy and asthmatic immune responses. Dysregulation of microbiota-related immunological and metabolic processes impacts the onset of asthma, its clinical characteristics and treatment response.47,48Antibiotic treatment and changes of the microbiome, especially early in life, are an important field of study since the microbiome has been associated with the health status of individuals in numerous diseases, including asthma.49 1-year old children that had an immature microbiome were shown to have a higher risk to develop asthma later in life if their mother was asthmatic as well.50A recent prospective study studied the connection between the gut microbiota and the development of asthma in wheezing preschool children. No connection to the richness of microbes nor species diversity was found, but an increase in bacteria of the genera Escherichia andGemminger at ages 2-4 in children that were diagnosed as asthmatics later on was reported.51 Lee et al. 52investigated the differences in the microbiome between young adults and elderly asthmatic and non-asthmatic individuals. They found an upregulation in genes, such as relative abundances of microbiome genes associated with the pentose phosphate pathway, lipopolisaccaride biosynthesis, flagellar assembly, and bacterial chemotaxis, and nitric oxide production were higher in asthmatics than in non-asthmatics. that could be related to increased inflammation and colonization of bacteria in young adult asthma patients. Furthermore, genes that could be related to the reduction of inflammation and degradation of air pollutants were higher in non-asthmatics of both age groups. In another study the authors showed a reduction in prostaglandin E2 (PGE2) in the asthma group, and an upregulation of the molecules that could be associated to airway inflammation such has arachidonic acid metabolites, lysine residues, and glycosaminoglycans.53 Together these data suggest that alterations in the composition and function of the upper airway microbiome could influence asthma pathogenesis and that specific effects can distinguished based on the age groups.
Probiotic bacteria interventions to prevent and to treat airway and allergic diseases are currently being evaluated. In a mouse model of asthma, Spacova et al.54 used different strains of and intranasally administrations of Lactobacillus rhamnosus to observe the preventive effects of probiotics. Only L. rhamnosusGG strain treatment lead to a reduction in BAL eosinophil counts, lung IL‐5 and IL‐13 levels, and in airway hyperreactivity. Thus, preventing the development of birch pollen-induced allergic asthma by probiotics is strain-specific. Ingestion of bacterial lysate has also been proposed to asthma. However, when extracts of Escherichia coli andEnterococcus faecalis were introduced into the diet of newborns, no significant effect on the occurrence of asthma, atopic dermatitis, AR or sensitization to allergens was observed in 6-11-year-old children.55
Pulmonary microbial dysbiosis can influence the inflammation status of the host. The dysbiosis can be inherited, if the mother was treated with antibiotics during the pregnancy resulting in higher asthma rates in the offspring as shown by Alhasan et al.56 Surprisingly, instead of the expected upregulation of type 2 cytokines in allergic offspring, a downregulation was found. Causalities are still unclear and will require specifically designed future studies to address this issue.
Microbial dysbiosis can also be induced by air pollution like tobacco smoke, while other pollutants influence the epithelium more directly. Eguiluz-Gracia et al57 reviewed the current understanding of indoor and outdoor air pollutants as well as the effects of climate change on human pulmonary health, highlighting how important clean air is for human health.