Influence of the gut and airway microbiome on asthma development and disease

There are ample data to suggest that early-life dysbiosis of both the gut and/or airway microbiome can predispose a child to develop along a trajectory toward asthma. Although individual studies show clear associations between dysbiosis and asthma development, it is less clear what (collection of) bacterial species is mechanistically responsible for the observed effects. This is partly due to issues related to the asthma diagnosis and the broad spectrum of anatomical sites, sample techniques, and analysis protocols that are used in different studies. Moreover, there is limited attention for potential differences in the genetics of individuals that would affect the outcome of the interaction between the environment and that individual. Despite these challenges, the first bacterial components were identified that are able to affect the transcriptional state of human cells, ergo the immune system. Such molecules could in the future be the basis for intervention studies that are now (necessarily) restricted to a limited number of bacterial species. For this transition, it might be prudent to develop an ex vivo human model of a local mucosal immune system to better and safer explore the impact of such molecules. With this approach, we might move beyond association toward understanding of causality. Benralizumab treatment in children demonstrated predictable PK parameters and a reassuring safety profile, consistent with previous studies in adolescents and adults. Treatment with benralizumab resulted in a near-complete reduction in blood eosinophil counts from baseline. Exploratory clinical outcomes indicated numerical improvements in FEV1, CGIC, and PGIC-IA responses, as well as ACQ-IA score and exacerbation rates.image