Microbial dysbiosis and childhood asthma development: Integrated role of the airway and gut microbiome, environmental exposures, and host metabolic and immune response.

Asthma is a chronic and heterogeneous respiratory disease with many risk factors that typically originate during early childhood. A complex interplay between environmental factors and genetic predisposition is considered to shape the lung and gut microbiome in early life. The growing literature has identified that changes in the relative abundance of microbes (microbial dysbiosis) and reduced microbial diversity, as triggers of the airway-gut axis crosstalk dysregulation, are associated with asthma development. There are several mechanisms underlying microbial dysbiosis to childhood asthma development pathways. For example, a bacterial infection in the airway of infants can lead to the activation and/or dysregulation of inflammatory pathways that contribute to bronchoconstriction and bronchial hyperresponsiveness. In addition, gut microbial dysbiosis in infancy can affect immune development and differentiation, resulting in a suboptimal balance between innate and adaptive immunity. This evolving dysregulation of secretion of pro-inflammatory mediators has been associated with persistent airway inflammation and subsequent asthma development. In this review, we examine current evidence around associations between the airway and gut microbial dysbiosis with childhood asthma development. More specifically, this review focuses on discussing the integrated roles of environmental exposures, host metabolic and immune responses, airway and gut microbial dysbiosis in driving childhood asthma development.