Abstract
According to the World Health Organization (WHO) asthma is a chronic disease affecting 235 million people worldwide. The disease is characterized by airway inflammation, airway hyperresponsiveness and airway narrowing. House dust mites (HDM) are common allergens that can induce allergic diseases like asthma. Current treatment, using corticosteroids, is not sufficient,
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therefore, novel preventive and/or therapeutic approaches are needed for asthmatic patients. Different animal and human studies showed that the development of asthma is associated with changes in the intestinal microbiota. Specific non-digestible oligosaccharides (NDO) are selectively fermented in the intestine supporting the growth and/or activity of beneficial bacteria such as bifidobacteria and lactobacilli. In this thesis, results are presented on the beneficial effects of dietary interventions with several NDO either or not in combination with a beneficial bacterium (Bifidobacterium breve M-16V, BB) on the development of airway allergy using a murine HDM-induced asthma model. The following dietary interventions were studied: a diet containing 1% galacto-oligosaccharides (GOS) alone, a combination of GOS with sialyllactose (GS), a combination of GOS/long-chain fructo-oligosaccharides (GF) or a combination of long-chain fructo-oligosaccharides and short-chain fructo-oligosaccharides (FF) either or not combined with BB (GFBB, FFBB). In addition, in several studies the preventive effects of dietary intervention were compared with a standard therapeutic glucocorticosteroid treatment on HDM-allergic asthma features in mice. The findings in this thesis demonstrate that dietary NDO partially prevent the development of HDM-induced allergic asthma. Immune modulation using dietary interventions with GF, FF either or not combined with BB, and the GOS diet alone was found to suppress airway eosinophilia, a major hallmark of allergic airway inflammation. Dietary NDO, and in particular GOS, were found to suppress the HDM-induced release of epithelial and/or dendritic cell-derived cytokines and chemokines T helper 2 cell and/or possibly innate lymphoid cells type 2-related cytokines resulting in reduced inflammatory cell numbers in the lung often in association with improvement of the lung function. The suppressive effect of GOS on airway eosinophilia was lost after regulatory T-cell depletion, suggesting these cells to be involved in the protective effect of GOS. Furthermore GOS was found to enhance the efficacy of glucocorticosteroid treatment in suppressing airway inflammation. In conclusion, this thesis highlights the efficacy of NDO and provides insight in the mechanisms of action of in particular GOS in the prevention of HDM-induced asthma in mice. Future studies are warranted to determine the applicability of specific NDO in the prevention and/or treatment of human asthma.
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