Study of asthma prevention and treatment with the administration of viable and heat-killed Saccharomyces cerevisiae in a murine model of allergic asthma

Abstract

Background: The prevalence of asthma has increased in children and in communities that adopt a Western lifestyle and become more urbanized. The hygiene hypothesis suggests that exposure to infections early in life can reduce the risk of asthma and other allergic diseases. Probiotics are live microorganisms that confer a health benefit to the host. Treatment with Saccharomyces cerevisiae protected mice against intestinal infections, prevented bacterial translocation and increased IL-10 production. Administration of Beta-1-3 Glucan, a polysaccharide extracted from fungi and yeasts such as S. cerevisiae, reduced symptoms of allergic rhinitis and increased IL-10 production in asthmatic children. There is no study of S. cerevisiae in the prevention or treatment of asthma. Objective: Evaluate the effects of viable and heat-killed S. cerevisiae oral administration in prevention and treatment of asthma and the mechanisms involved. Methods: Balb/c mice will be used in the study. Initially, a dose-response curve will be realized to determine the probiotic dose. Viable and heat-killed S. cerevisiae will be administered before and after sensitization with ovalbumin. After sensitization and challenge, mice will be ventilated and in vivo measurements of bronchial hyperresponsiveness will be realized. Bronchoalveolar lavage will be collected to quantify total and differential cell counts and cytokine levels by ELISA (IL-4, IL-5, IL-10, IL-13, IFN-gamma, TNF-alpha and TGF-beta). Histochemistry will be performed in the lungs to quantify inflammation, collagen and mucus. Real time PCR will be realized in lung tissue to measure inflammatory cytokine, such as IL-4, IL-5, IL-10, IL-13, IFN-gamma, TNF-alpha and TGF-beta. Flow cytometry will be realized to quantify regulatory T lymphocytes. Regulatory T lymphocytes will be isolated, cultured and there function will be assessed by proliferation assay and cytokine measurement of cell culture supernatant. Significance: Considering the hygiene hypothesis, the mechanisms of action and safety of probiotics, it is expected that administration of Saccharomyces cerevisiae will reduce airway inflammation, hyperresponsiveness and remodeling, and could be considered for asthma treatment. (AU)