The Combination Therapy of Dietary Galacto-Oligosaccharides With Budesonide Reduces Pulmonary Th2 Driving Mediators and Mast Cell Degranulation in a Murine Model of House Dust Mite Induced Asthma

Abstract

Background: Dietary non-digestible galacto-oligosaccharides (GOS) suppress allergic responses in mice sensitized and challenged with house dust mite (HDM). Budesonide is the standard therapy for allergic asthma in humans but is not always completely effective.Aim: To compare the efficacy of budesonide or different doses of GOS alone or with a combination therapy of budesonide and GOS on HDM-allergic responses in mice.Methods:BALB/c mice were sensitized and challenged with HDM, while fed a control diet or a diet supplemented with 1 or 2.5 w/w% GOS, and either or not oropharyngeally instilled with budesonide. Systemic and local inflammatory markers, such as mucosal mast cell protease-1 (mMCP-1) in serum, pulmonary CCL17, CCL22, and IL-33 concentrations and inflammatory cell influx in the bronchoalveolar lavage fluid (BALF) were determined.Results: Budesonide or GOS alone suppressed the number of eosinophils in the BALF of HDM allergic mice whereas budesonide either or not combined with GOS lowered both eosinophil and lymphocyte numbers in the BALF of HDM-allergic mice. Both 1 w/w% and 2.5 w/w% GOS and/or budesonide suppressed serum mMCP-1 concentrations. However, budesonide nor GOS alone was capable of reducing Th2 driving chemokines CCL17, CCL22 and IL-33 protein levels in supernatants of lung homogenates of HDM allergic mice, whereas the combination therapy did. Moreover, IL-13 concentrations were only significantly suppressed in mice treated with budesonide while fed GOS. A similar tendency was observed for the frequency of GATA3+CD4+ Th2 and CD4+RORγt+ Th17 cells in the lungs of the allergic mice.Conclusion: Dietary intervention using GOS may be a novel way to further improve the efficacy of anti-inflammatory drug therapy in allergic asthma by lowering Th2 driving mediators and mast cell degranulation.

25‐Hydroxycholesterol metabolism is altered by lung inflammation, and its local administration modulates lung inflammation in mice

“…For drug treatment, 25‐OHC (1 and 10 mg/kg) or budesonide (0.5 mg/kg 25 ) in vehicle (saline–DMSO–Tween 80 [98.9:1:0.1, v/v/v]) were administered intranasally 6 hours before HDM instillation (Days 9‐12). On Day 13, the treatments (25‐OHC or budesonide) were administered 24 hours prior to euthanasia of the mice and assessment of the outcomes.…”

Crude Turmeric Extract Improves the Suppressive Effects of Lactobacillus rhamnosus GG on Allergic Inflammation in a Murine Model of House Dust Mite-Induced Asthma

“…The IL-33 secretion along with the allergen stimulation can activate ILC2 and DCs. Activated DCs are able to polarize naïve T helpers to Th2 in the CCL17 saturated environments (57). Our treatments specially HDM-TP-LGG E5 proficiently mitigate the concentration of CCL17 leading to the decreasing of Th2 frequency (Figure 7).…”

“…This effect was more striking in synbiotic groups (Figure 7). Beyond this effect on Th2-mediated cytokines, the combination therapies also mitigate the intensity of CD196 + RORγ + Th17 cells (Figure 7) which is known to be elevated in asthmatic peoples (57). Our treatments specially probiotics reduces the number of eosinophils in BALF.…”

SUL-151 Decreases Airway Neutrophilia as a Prophylactic and Therapeutic Treatment in Mice after Cigarette Smoke Exposure

“…Total numbers of BALF cells were counted using a Bürker-Türk chamber and differential BALF cell counts of macrophages, neutrophils, lymphocytes, and eosinophils were determined on cytospin preparations stained by Diff-Quik (Merz & Dade A.G., Düdingen, Switzerland). Differential cell counts were performed with at least 200 cells [ 52 ]. The first ml BALF was used for TNF-α measurements by ELISA (Mouse TNF-α ELISA kit, Thermo Fisher Scientific, Waltham, MA, USA) according to the manufacturer’s instructions.…”