Oral Lactobacillus rhamnosus GR-1 prevents airway function deterioration and promotes gut microbiota resilience in a mouse model of allergic asthma

Allergic asthma is a highly prevalent inflammatory disease of the lower airways, clinically characterized by airway hyperreactivity, mucus hypersecretion and deterioration of airway function. Probiotic bacteria with intrinsic immunomodulatory properties are increasingly being explored to prevent asthma development and reduce asthma symptoms, alone or in combination with other available treatments, such as allergen-specific immunotherapy. In this study, wild-type and recombinant probiotic Lactobacillus rhamnosus GR-1 strains designed to produce the major birch pollen allergen Bet v 1 were tested as oral preventive treatment of experimental allergic asthma in mice. A significant improvement in airway function, including airway hyperreactivity, was obtained after administration of wild-type and recombinant Bet v 1-producing L. rhamnosus GR-1. Signs of airway inflammation (i.e. airway total cell counts, lymphocyte counts and lung IL-1b levels) were significantly reduced by recombinant L. rhamnosus GR-1 producing Bet v 1, while effects of wild-type L. rhamnosus GR-1 were less pronounced. Interestingly, no reduction specifically in Type 2 allergic sensitization or inflammation was observed, suggesting the involvement of additional mechanisms. Furthermore, asthma development was linked to a shift in gut microbiome composition, which correlated with the severity of allergic sensitization, airway inflammation and airway hyperreactivity. Importantly, in the groups that received wild-type and recombinant L. rhamnosus GR-1, this asthma-associated shift in gut microbiome composition was not observed. These data demonstrate that L. rhamnosus GR-1 can prevent airway hyperreactivity in allergic asthma, and that there is an additional effect of the Bet v 1-producing L. rhamnosus GR-1 in preventing airway inflammation. The beneficial effects of L. rhamnosus GR-1 strain correlate with increased gut microbiome resilience, which in turn is linked to the protection of airway function and thus further adds support to the existence of a gut-lung axis.