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.
Highlights
Asthma is a chronic disease affecting 235 million people worldwide
Murine House dust mite (HDM) allergic asthma models are commonly used to mimic some of the human features of asthma as they show airway inflammation and pulmonary cytokine release similar to humans [34, 35]
In the current study the combination of GOS and budesonide almost completely abolished eosinophil and lymphocyte numbers, which was associated with improved airway resistance, lower inflammatory mediator release and reduced mast cell degranulation. mMCP-1 is released by mast cells in the tissue upon allergen challenge, becomes available locally and as a reflection can be measured back in the serum [36,37,38] (Figure 6)
Summary
Asthma is a chronic disease affecting 235 million people worldwide. The disease is characterized by airway hyperresponsiveness, airway narrowing and airway inflammation containing high numbers of eosinophils [1, 2]. DC release chemokines such as CCL17 and CCL22 known to drive the development of Th2 effector responses from naïve T cells in the mediastinal lymph nodes These Th2 cells will migrate to the pulmonary mucosa and like ILC2 produce IL-13 and drive allergic sensitization and symptoms of allergic airway inflammation [4, 6, 7]. Different animal and human studies indicated changes in the intestinal microbiota may contribute to development of asthma [12,13,14,15] Specific nondigestible oligosaccharides such as galacto-oligosaccharides (GOS) are selectively fermented in the intestine resulting in support of growth and/or activity of bifidobacteria and Abbreviations: BALF, bronchoalveolar lavage fluid; DC, dendritic cell; FOS, fructo-oligosaccharide; GOS, galacto-oligosaccharide; HDM, house dust mite; ILC2, group 2 innate lymphoid cell; OVA, ovalbumin. Budesonide is the standard therapy for allergic asthma in humans but is not always completely effective
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