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.