Lung microbiota analyses in asthma mouse model

Background: Asthma is a frequent chronic inflammatory bronchial disease affecting more than 300 million patients worldwide, 70% of whom secondary to allergy. The diversity of asthmatic endotypes contributes to their complexity. Many factors, such as the environment, allergen sensitization pathways associate with microbiota, influence asthma natural course and explain its phenotypic heterogeneity. Here, we compared a mouse model of house dust mite (HDM)-induced allergic asthma sensitized via various routes for the clinical features of asthma, immune responses, the lung barrier and dysbiosis. Method: Mice were sensitized HDM by oral, nasal or percutaneous routes. Lung function, barrier integrity, immune response and microbiota composition were analyzed. Results: Severe impairment of respiratory function was observed in the mice sensitized by the nasal and cutaneous paths. It was associated with epithelial dysfunction characterized by an increased permeability secondary to junction protein disruption. Conversely, such sensitization paths induced a mixed eosinophilic and neutrophilic inflammatory response with high IL-17 airways secretion. In contrast, oral sensitized mice showed a mild impairment of respiratory function. Epithelial dysfunction was lighter with increased mucus production but conserved epithelial junctions. Lung Th2 and eosinophilic inflammation were observed. Considering lung microbiota, sensitization provoked a significant loss diversity. At the genus level, Cutibacterium, Acinetobacter, Streptococcus and Lactobacillus were found to be modulated according to the sensitization pathway. An increase in anti-inflammatory microbiota metabolites was observed in the oral group. Conclusion: Our study highlights the strong involvement of the sensitization route in allergic asthma physiopathology and the critical phenotypic diversity in a mouse model.