Lung microbiota analyses in asthma mouse model

<p class="MsoNormal"><span class="Titre2Car"><span>Background:</span></span><span> Asthma is a frequent chronic inflammatory bronchial disease affecting more than 300 million </span><span>patients worldwide, 70% of whom secondary to</span><span> allergy. The diversity of asthmatic endotypes contributes to </span><span>their</span><span> complexity. Many factors, </span><span>such </span><span>as </span><span>the </span><span>environment, allergen sensitization pathways associate with microbiota, influence asthma natural course and explain its phenotypic heterogeneity. Here</span><span>,</span><span> we compared </span><span>a </span><span>mouse model of house dust mite (HDM)-induced allergic asthma sensitized via various routes for </span><span>the </span><span>clinical features of asthma, immune responses, the lung barrier and dysbiosis.</span></p> <p class="MsoNormal"><span class="Titre2Car"><span>Method:</span></span><span> Mice were sensitized HDM by</span> <span>oral, nasal or percutaneous routes. Lung function, barrier integrity, immune response and microbiota composition were analyzed.</span></p> <p class="MsoNormal"><span>Results: </span><span>Severe </span><span>impairment of respiratory function </span><span>was</span><span> observed </span><span>in</span><span> 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, </span><span>such sensitization paths induced</span><span> a </span><span>mixed</span><span> eosinophilic and neutrophilic inflammatory response with high IL-17 airways secretion. </span><span>In contrast, oral </span><span>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 </span><span>were observed</span><span>. Considering lung microbiota, sensitization provoked a significant loss diversity. </span><span>At</span><span> the genus level, </span><span>Cutibacterium, Acinetobacter, Streptococcus and Lactobacillus</span><span> were found to be modulated according to the sensitization pathway. An increase </span><span>in</span><span> anti-inflammatory microbiota metabolites </span><span>was</span><span> observed in the </span><span>oral group</span><span>. </span></p> <p class="MsoNormal"><span>Conclusion: Our study highlights the strong involvement of the sensitization route in allergic asthma physiopathology and the critical </span><span>phenotypic</span><span> diversity in a mouse model.</span></p>