Biomarkers linked to Microbiome and Asthma
An enormous variety of microbes colonize mucosal body surfaces and these
microbes are organized within complex community structures, utilizing
nutrients from other microbes, host secretions and the diet. Modern
lifestyles, medications and social interactions have fundamentally
altered and disrupted the human microbiome metacommunity and, as a
consequence, risk of immune-mediated diseases such as allergy and
asthma.49,50 The mechanisms that mediate host-microbe
communication are highly sophisticated and are being intensely
investigated by many research groups across the world. However, there is
accumulating evidence that microbiome composition and metabolic
activities within the gut and the airways can influence asthma
pathogenesis.51-53 Here, we summarize some of the key
recent findings that identify specific microbes or associated
metabolites that may be useful as biomarkers to predict asthma risk,
asthma severity or guide existing or novel therapies.
Alterations in the gut microbiota within the first year of life have
been associated with asthma risk in multiple birth cohort
studies.19 The lower relative abundance of genera
including Lachnospira , Veillonella ,Faecalibacterium , Rothia , Bifidobacterium andAkkermansia in the gut during early life have been associated
with the development of asthma.54,55 While fewer
studies have examined pre-school children (2-4 years of age), a recent
study in this age group demonstrated that certain bacterial genera
within the gut were still associated with wheezing (Collinsellaand Dorea ) or subsequent development of asthma (Gemmigerand Escherichia ).56 In addition to the gut
microbiota, studies are also showing changes in the microbial
populations of the airways. Microbial diversity and the relative
abundances of Veillonella and Prevotella in the airways at
age one month were associated with asthma by age 6
years.57 Interestingly, higher relative abundance of
these bacteria was associated with reduced TNF-α and IL-1β and increased
CCL2 and CCL17 within the airways. A switch from aCorynebacterium and Dolosigranulum cluster in the
upper-airways to a Moraxella cluster was associated with a higher
risk of severe asthma exacerbation in children with
asthma.58 In adults, increased relative abundance of
the phylum Proteobacteria (including Haemophilus ,Comamonadaceae , Sphingomonadaceae ,Nitrosomonadaceae , Oxalobacteraceae andPseudomonadaceae ) is often associated with asthma or with worse
asthma control.59 Microbial changes within the gut,
upper and lower airways of adult asthma patients are magnified in obese
asthma patients and in those with severe disease.60Bronchoalveolar lavage levels of IL-5 and eosinophils correlated with a
variety of microbes within the airways. Of note, severe asthma
negatively correlated with fecal Akkermansia levels and oral
administration of Akkermansia to murine models significantly
reduced airway hyper-reactivity and airway inflammation (Figure 2).
In addition to microbiota composition, microbial metabolites may also be
useful biomarkers in asthma. The fecal metabolome of children at
increased risk of asthma contained increased levels of pro-inflammatory
metabolites, among which 12, 13 DiHOME was able to induce IL-4
production in CD4+T cells and decreased the abundance
of Tregs.55 High levels of short chain fatty acids
(SCFAs), such as butyrate and propionate, at one year of age were
associated with reduced risk of atopic sensitization and asthma by
school age.61 Multiple immune modulatory effects have
been described in murine models for SCFAs, which include the promotion
of Treg development and the inhibition of pulmonary ILC2 functions and
subsequent development of airway hyper-reactivity.62In adults, an increased abundance of histamine secreting bacteria were
observed within the gut of patients with asthma, while disease severity
correlated with high levels of the histamine secreting microbeMorganella morganii .63 Murine models have
demonstrated that bacterial-derived histamine within the gut can
influence inflammatory responses within the lungs.64
In the future, the application of recent advances in metagenomic
sequencing technologies and bioinformatics will likely lead to the
identification of novel functional traits and metabolites within the gut
and airway microbiome of asthma patients.65 In
addition, future asthma studies should include the microbiome as
potential biomarkers that predict or associate with responses to
biologics, as already observed for Faecalibacterium ,Bifidobacterium and Akkermansia that associate with
immunotherapy responses in certain groups of cancer
patients.66