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.