The mechanism or mechanisms driving atopic asthma initiation: The infant respiratory microbiome moves to center stage

It is acknowledged that key events that determine risk for the development of allergic disease frequently occur years before manifestation of symptoms. Recent culture-based studies, in combination with population-wide bacterial metagenomic data, suggest that parallel bacterial interactions may contribute to disease development. Holt reviews these and related issues of immune competence in infancy (J Allergy Clin Immunol 2015; 136(1): 15-22).

A number of factors specific to  infancy can contribute to disease development. Prospective tracking of postnatal IgE titres in serum samples collected over the first five years of life strongly suggests IgE antibody production against aeroallergens rarely begins before the age of six months. Airway mucosal dendritic cells (AMDC) transmit aeroallergen-specific signals from the airway mucosal surface to the central immune system and program the balance between the Th2 and T regulatory cell components of the immunological memory that results. The immaturity of this network in infants is likely a risk factor for early respiratory infection, itself a risk factor for early atopic asthma.

The focus on respiratory pathogens that contribute to the immunopathogenesis of atopic asthma has in the past been almost exclusively on viral pathogens: respiratory syncitial virus (RSV) and human rhinovirus (HrV). Emerging studies include consideration of the role of bacterial pathogens. Data suggests qualitative and quantitative differences in the lower airway bacterial populations of asthmatic children, including the mix of the strains present and the overall bacterial burden. The findings call for an accurate understanding of the full spectrum of strains that constitute the respiratory tract microbiome, particularly  nasopharyngeal microbial populations which function as a resevoir from which seeding into the lower airways occurs, in terms of population level and dynamics, across the average age range for asthma onset. The Perth CAS cohort study of 234 infants has provided the first foundation for this work. Questions, such as whether the replacement of commensal bacteria species in the nasopharyngeal microbiome of infants with known pathogens precede or result from local viral infection, remain to be answered.