- Title
- Dietary fibre as a modulator of inflammation in asthma
- Creator
- McLoughlin, Rebecca Frances
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2019
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- Asthma is a common chronic respiratory disease, affecting approximately 334 million people worldwide. Asthma management places a substantial economic burden on both the health system and the individual. In Australia, it has been estimated that asthma management costs >$600million per year, 50% of which is attributed to inhaled corticosteroids which are the mainstay of asthma therapy. However, long-term, high dose treatment can predispose individuals to side effects such as osteoporosis, hypertension, insulin resistance and neuropsychiatric effects, and some patients respond poorly. Evidently new ways to improve asthma management are needed. While genetics play an important role in asthma development and progression, it is apparent that there is an association between asthma prevalence and the westernised lifestyle, including the western diet. Westernisation of diets has led to reduced dietary fibre intake. This is undesirable as dietary fibre has been shown to be inversely associated with the severity of airway inflammation and positively associated with lung function in asthma. The anti-inflammatory benefits of dietary fibre intake have been ascribed to the effects of soluble fibres, which are fermented by beneficial gut bacteria in the colon generating biologically active by-products, including the short chain fatty acids (SCFA). SCFAs are suggested to have anti-inflammatory effects via mechanisms including the activation of G protein-coupled receptor (GPR) 41 and GPR43 in immune cells, and the inhibition of histone deacetylase (HDAC) enzyme activity. This thesis aims to: examine the available evidence for the effect of SCFAs, prebiotics (soluble fibre) and synbiotics (prebiotic and probiotic combinations) on systemic inflammation in humans; examine the effects of soluble fibre supplementation, with and without a probiotic, in adults with asthma; investigate the effects of soluble fibre intake (via fruit and vegetable intake) in children with asthma; and to examine molecular and epigenetic mechanisms that are modulated by soluble fibre, including HDAC enzyme activity and GPR41/43 and HDAC1-11 gene expression. Chapter 2 presents the current evidence for the effect of SCFAs, prebiotics and synbiotics on systemic inflammation in humans. This systematic literature review and meta-analysis revealed that the evidence from individual studies is conflicting, with approximately 50% of included studies reporting a significant decrease in more than one inflammatory biomarker. Nonetheless, results of the meta-analyses of combined studies provide evidence to support the systematic anti-inflammatory benefits of prebiotic and synbiotic supplementation. In chapter 4, the effects of soluble fibre supplementation, with and without a probiotic, in adults with asthma (n=17) were investigated. Following 7 days of soluble fibre (inulin) supplementation, we observed a reduction in airway eosinophils (Δ -1.0 [-2.5, 0.0], p=0.006), an improvement in asthma control (Δ -0.35 [-0.50, -0.13], p=0.006) and a trend towards improvement in lung function (Δ 1 [-0.5, 4], p=0.131), in adults with stable asthma. No significant changes in clinical outcomes or airway inflammation were observed with inulin+probiotic supplementation. Down regulation of sputum HDAC9 gene expression (p=0.008) was identified as a potential anti-inflammatory mechanism of soluble fibre in asthma, which was strongest in individuals with eosinophilic airway inflammation. Chapter 5 investigated the effect of soluble fibre intake (via fruit and vegetable intake) in children with asthma (n=47). In this randomised controlled trial (RCT), participants were randomised to either a high or low fruit and vegetable diet for 6 months. Increasing fruit and vegetable intake in children with asthma was found to improve lung function. Furthermore, in the absence of the protective effect of a high fruit and vegetable diet, over a 6 month period, systemic inflammation (CRP) increased in asthmatic children (Δ 0.37 [-0.04, 1.58], p=0.04). Down regulation of GPR41 gene expression (Δ -0.17 [-3.64, 0.47], p=0.01) and increased HDAC activity (Δ 0.80 [-0.26, 1.71], p<0.01) are suggested to contribute to this increase in systemic inflammation. Overall, the research conducted as part of this thesis has contributed to the understanding of the benefits of soluble fibre intake in both adults and children with asthma, and the potential anti-inflammatory mechanisms involved. Delivery of soluble fibre, in both supplemental form and by increasing fruit and vegetable intake, has led to improvements in clinical outcomes and inflammatory pathways, in adults and children respectively. Hence we conclude that soluble fibre supplementation is a promising new therapeutic approach for asthma.
- Subject
- asthma; inflammation; soluble fibre; short chain fatty acid
- Identifier
- http://hdl.handle.net/1959.13/1401267
- Identifier
- uon:34885
- Rights
- Copyright 2019 Rebecca Frances McLoughlin
- Language
- eng
- Full Text
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| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT01 | Thesis | 3 MB | Adobe Acrobat PDF | View Details Download | ||
| View Details Download | ATTACHMENT02 | Abstract | 384 KB | Adobe Acrobat PDF | View Details Download |