Microbiota in allergy and asthma and the emerging relationship with the gut microbiome

Abstract

Asthma and atopy, classically associated with hyper-activation of the T helper 2 (Th2) arm of adaptive immunity, are among the most common chronic illnesses worldwide. Emerging evidence relates atopy and asthma to the composition and function of the human microbiome, the collection of microbes that reside in and on and interact with the human body. The ability to interrogate microbial ecology of the human host is due in large part to recent technological developments that permit identification of microbes and their products using culture-independent molecular detection techniques. In this review we explore the roles of respiratory, gut, and environmental microbiomes in asthma and allergic disease development, manifestation, and attenuation. Though still a relatively nascent field of research, evidence to date suggests that the airway and/or gut microbiome may represent fertile targets for prevention or management of allergic asthma and other diseases in which adaptive immune dysfunction is a prominent feature.

Fig. 1. Molecular tools for interrogating microbiome composition and function

DNA, RNA, Protein and Metabolite fractions of the samples may be interrogated using next-generation sequencing and mass spectroscopy platforms to assess microbiome composition and function.

Fig. 2. Very early life exposures influence asthma and allergy development

Oropharyngeal colonization of neonates by Streptococcus, Haemophilus or Moraxella species at 4 weeks of age is associated with development of recurrent wheeze. Infants colonized at 12-months with the same species were not at higher risk. Dysbiotic neonatal (3 week old) gut microbiomes enriched with Escherichia coli or Clostridium difficile are at significantly higher risk for childhood atopy development, which is typically characterized by elevated serum IgE levels.

Fig. 3. Adaptive immune modulation in the gut and airways through gastrointestinal microbiome manipulation

A. Lactobacillus johnsonii supplementation leads to decreased numbers of activated dendritic cells (DC) in the mesenteric lymph nodes (MLN) and a parallel decrease in Th2 cytokine expression IL-4, IL-5, and IL-13, IL-17 and DCs in the lungs. B. Mice supplemented by a cocktail of Clostridium IV and XIV species exhibit an increase in colonic T-regulatory cells and the anti-inflammatory cytokine IL-10, and were protected against ovalbumin-induced allergic diarrhea in part due to decreased levels of serum OVA-specific IgE and IL-4. C. Feeding propionate to mice resulted in circulation of short-chain fatty acids (SCFAs), associated with increased common and macrophage dendritic cell precursor cells (Lin⁻C⁻Kit^Lo Flt3⁺ CDPs and Lin⁻C⁻Kit^Hi Flt3⁺ MDPs respectively), which is associated with reduced DC proliferation and Th2 reactivation in the lungs.