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Parenti, C. 
ORCID: 0000-0003-3439-5816,
2023.
The role of inflammation, gut permeability and body weight in asthma: from molecular to human prebiotic interventions.
PhD, Nottingham Trent University.
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Abstract
Asthma is an inflammatory disease of the airways affecting 5.4 million people in the UK. Furthermore, obesity increases the risk of developing asthma is associated with worse symptoms and less response to medication. Both asthma and obesity are characterised by increased systemic inflammation that may be exacerbated by poor gut barrier integrity. Increased gut permeability allows endotoxin such as lipopolysaccharide (LPS) to translocate into the blood stream further increasing inflammation and indirectly exacerbating asthma symptoms. Common strategies to treat asthma are limited to targeting symptoms, rather than of the underlying inflammation. Novel strategies that may help ameliorate inflammation are short chain fatty acids (SCFA), end-products of gut bacteria fermentation of dietary substrates such as prebiotics, which appear to have anti-inflammatory properties and provide benefit at molecular and systemic level.
Therefore, a series of studies have been conducted to evaluate whether SCFA (acetate, butyrate, propionate) can mitigate LPS associated damage in organelles that leads to inflammation (mitochondria) at cellular level. Then, a human prebiotic intervention trial, which could indirectly increase circulating SCFAs level, was conducted to explore whether nutritional supplementation could be effective in reducing asthma symptoms and inflammatory, metabolic and permeability markers. Moreover, the effect of obesity and gut permeability on asthma severity was evaluated in cohorts of patients across asthma disease severity. Finally, to support future disease diagnosis a pilot study was conducted to explore difference in metabolic profiling between patients with and without asthma.
The outcome of these studies demonstrates that SCFA limit LPS induced damage in airway cells. The administration of prebiotics in adults with well-controlled asthma revealed a potential improvement in markers of metabolic health and inflammation. Furthermore, patients with obesity and asthma exhibit greater gut permeability which may represent a contributing factor to disease severity. Finally, through a metabolomic pilot study this thesis has revealed a potential metabolite profile that contributes to cluster separation between asthma and healthy controls.
Taken together the data suggested that increasing circulating SCFA via administration of prebiotic may provide an adjunctive tool to reduce inflammatory and metabolic damage at cellular level and in patients with asthma. Moreover, evaluation of the impact of obesity and gut permeability in asthma suggested that a broader range of approaches are needed to better characterize the pathophysiology of disease and improve future diagnosis and treatment.
| Item Type: | Thesis | ||||||||||||||||
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| Creators: | Parenti, C. | ||||||||||||||||
| Contributors: |
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| Date: | November 2023 | ||||||||||||||||
| Rights: | This work is the intellectual property of the author. You may copy up to 5% of this work. for private study, or personal, non-commercial research. Any re-use of the information contained within this document should be fully references, quoting the author, title, university, degree level and pagination. Queries or requests for any other use, or if a more substantial copy is required, should be directed in the owner(s) of the Intellectual Property Rights. | ||||||||||||||||
| Divisions: | Schools > School of Science and Technology | ||||||||||||||||
| Record created by: | Jeremy Silvester | ||||||||||||||||
| Date Added: | 02 Aug 2024 14:14 | ||||||||||||||||
| Last Modified: | 02 Aug 2024 14:14 | ||||||||||||||||
| URI: | https://irep.ntu.ac.uk/id/eprint/51888 |
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