Lactobacillus rhamnosus probiotic prevents airway function deterioration and promotes gut microbiome resilience in a murine asthma model

Abstract

Allergic asthma is a highly prevalent inflammatory disease of the lower airways, clinically characterized by airway hyperreactivity and deterioration of airway function. Immunomodulatory probiotic bacteria are increasingly being explored to prevent asthma development, alone or in combination with other treatments. In this study, wild-type and recombinant probiotic Lactobacillus rhamnosus GR-1 were tested as preventive treatment of experimental allergic asthma in mice. Recombinant L. rhamnosus GR-1 was designed to produce the major birch pollen allergen Bet v 1, to promote allergen-specific immunomodulation. Administration of wild-type and recombinant L. rhamnosus GR-1 prevented the development of airway hyperreactivity. Recombinant L. rhamnosus GR-1 also prevented elevation of airway total cell counts, lymphocyte counts and lung IL-1β levels, while wild-type L. rhamnosus GR-1 inhibited airway eosinophilia. Of note, a shift in gut microbiome composition was observed after asthma development, which correlated with the severity of airway inflammation and airway hyperreactivity. In the groups that received L. rhamnosus GR-1, this asthma-associated shift in gut microbiome composition was not observed, indicating microbiome-modulating effects of this probiotic. These data demonstrate that L. rhamnosus GR-1 can prevent airway function deterioration in allergic asthma. Bet v 1 expression by L. rhamnosus GR-1 further contributed to lower airway inflammation, although not solely through the expected reduction in T helper 2-associated responses, suggesting involvement of additional mechanisms. The beneficial effects of L. rhamnosus GR-1 correlate with increased gut microbiome resilience, which in turn is linked to protection of airway function, and thus further adds support to the existence of a gut-lung axis.

Prevention and Management with Pro-, Pre and Synbiotics in Children with Asthma and Allergic Rhinitis: A Narrative Review

“…A beneficial effect of the administration of probiotics was suggested by showing that oral administration of Lactococcus lactis NZ9000 to rats resulted in a decrease in infiltration of pro-inflammatory leucocytes, mainly eosinophils and decreased lung IL-4 and IL-5 expression in the broncho-alveolar lavage and a reduced level of serum allergen-specific IgE [ 24 ]. Another study conducted in mice using Lactobacillus rhamnosus GR-1 significantly prevented airway hyperreactivity development and prevented microbiome disturbance in the asthmatic animals, supporting the existence of the gut–lung axis [ 25 ]. An interesting aspect is that most probiotics are given orally; however, a new approach was tested by giving probiotics ( Lactobacillus paracasei NCC2461 [ 26 ] and Lactobacillus rhamnosus GG [ 27 ] in mice through the nose and showed benefits in reducing inflammation of the lungs [ 28 ].…”

Probiotics reduce self-reported symptoms of upper respiratory tract infection in overweight and obese adults: should we be considering probiotics during viral pandemics?

“… 16 As such, one potential area for future exploration may be the potential impact of probiotics upon other human diseases for which cough is a predominant feature, including allergic diseases such as asthma; administration of a Lactobacillus rhamnosus resulted in lung protection in a murine allergic respiratory disease model, with the probiotic demonstrated to alter respiratory IL-1β levels, as well as airway total cell counts and lymphocyte counts. 43 …”

Impact of Probiotic Bacteria on Respiratory Allergy Disorders

“…Therefore, all activities leading to the maintenance or restoration of the microbiome may represent a new therapeutic approach. Recently it was shown that Lactobacillus rhamnosus GR-1 can alleviate the symptoms in the murine model of allergy ( Spacova et al, 2020 ). In the study, mice were supplemented with 10 10 CFU of bacteria four times per week through 6 weeks.…”