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Lester, P 
ORCID: https://orcid.org/0000-0002-8971-7504,
2022.
The gut microbiota in the pathophysiology of hyperpnoea-induced bronchoconstriction: investigating the effects of short and long-term prebiotic supplementation.
PhD, Nottingham Trent University.
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Paul Lester - Doctoral Thesis - Submission Copy - Post Viva.pdf - Published version Download (7MB) | Preview |
Abstract
In adults with allergic asthma, clinical and inflammatory parameters have been associated with features of gut microbial dysbiosis. This has led researchers to investigate whether the severity of asthma can be attenuated through gut-microbiota mediated nutritional interventions, such as prebiotics. Strikingly, following 3-weeks of supplementation with a galactooligosaccharide-based prebiotic, clinically relevant, participant perceivable improvements have been observed in adults with moderate-severe exercise-induced bronchoconstriction. However, given that gut bacterial composition has not been assessed in adults with EIB, it remains to be determined whether prebiotics attenuate the severity of EIB via the gut microbiota. Furthermore, the minimum, clinically important dose required to attenuate the severity of EIB remains to be determined. To address these questions, the current thesis investigated whether adults with EIB displayed features of gut microbial dysbiosis, and whether short-term and long-term supplementation with a low dose galactooligosaccharide-based prebiotic attenuated the severity of EIB.
The first experimental chapter (Chapter IV) investigated whether adults with moderate EIB displayed features of gut microbial dysbiosis through fluorescent in situ hybridisation (FISH). A total of seven (n = 7) adults with EIB, and seven (n = 7) controls took part. Participants provided a faecal sample to assess gut bacterial composition, a blood sample to assess markers of systemic inflammation, and completed the EVH protocol to determine the presence and severity of EIB. Despite significant increases in the percentage decrease in FEV1 post-EVH (median, IQR: 38, [26-41] vs. 6, [4-7%]; p = 0.002), and resting blood eosinophils (8 ± 2 vs. 4 ± 2%; p = 0.008), no features of gut microbial dysbiosis were reported in adults with moderate EIB across any bacterial groups when compared to controls (p > 0.05). It is possible the current method used to profile the gut microbiota lacked the required sensitivity to detect features of gut microbial dysbiosis. In contrast to the current method, previous research has used metagenomics-based approaches to profile the gut microbiota of adults with allergic asthma to the species and strain levels, identifying features of gut microbial dysbiosis. This study highlights the importance of using techniques capable of profiling the gut microbiota to the appropriate phylogenetic depth.
The second experimental chapter (Chapter V) investigated whether short-term (acute) supplementation with a single low dose galactooligosaccharide-based prebiotic (3.1g; HOST-DM059), attenuated the severity of EIB and markers of systemic inflammation. A total of eight (n = 8) adults with mild EIB took part. Following a double-blind, placebo-controlled, crossover design, participants completed two experimental trials. During each experimental trial, participants underwent baseline assessments of pulmonary function, and provided a blood sample to assess markers of systemic inflammation. A single dose of prebiotic or placebo was then administered prior to a 4-hour ingestion period. Following the ingestion period, participants repeated assessments of pulmonary function and provided a second blood sample before completing the EVH protocol. A third blood sample was obtained one-hour after the EVH protocol. When compared to placebo, short-term supplementation with a low dose galactooligosaccharide-based prebiotic did not attenuate the severity of EIB (21 ± 7 vs. 18 ± 7% decrease in FEV1 post-EVH; p = 0.092), or markers of systemic inflammation (2.1 ± 1.3 vs. 1.8 ± 0.7% blood eosinophils measured one-hour post EVH; p > 0.05).
The third experimental chapter (Chapter VI) investigated whether long-term supplementation with a low dose galactooligosaccharide-based prebiotic attenuated the severity of EIB (4-weeks, 3.1g/day-1; HOST-DM059). A total of nine (n = 9) adults with EIB, and eight (n = 8) controls took part. Following a double-blind, placebo-controlled, crossover design, participants completed a 10-week nutritional intervention, consisting of two, 4-week supplementation phases each separated by a 2-week washout period. During each experimental trial, participants provided a resting blood sample to assess markers of systemic inflammation and completed the EVH protocol. In the EIB group, long-term supplementation with a low dose galactooligosaccharide-based prebiotic did not attenuate the severity of EIB (22 ± 12 vs. 22 ± 10% decrease in FEV1 post-EVH; p > 0.05), or markers of systemic inflammation (3 ± 2 vs. 2 ± 1% resting blood eosinophils; p > 0.05). Furthermore, no changes were observed in the proportion of regulatory T cell subsets in adults with EIB following prebiotic supplementation, including Type-1 IL-10 producing TREG cells (1.5 vs. 1.4% of CD3+ CD4+ T Cells; p > 0.05), or naturally derived CD25+ FoxP3+ TREG cells (6.5 vs. 6.4% of CD3+ CD4+ T Cells; p > 0.05).
The current thesis provides novel contributions by suggesting that a minimum threshold may exist for prebiotic supplementation to induce clinically relevant, participant perceivable improvements in the severity of EIB. Future research should investigate the effects of baseline gut bacterial composition, EIB severity, and habitual dietary fibre intake on the responsiveness to prebiotic supplementation.
| Item Type: | Thesis |
|---|---|
| Creators: | Lester, P. |
| Contributors: | Name Role NTU ID ORCID |
| Date: | November 2022 |
| Rights: | This work is the intellectual property of the author. You may copy up to 5% of this Nottingham Trent University work for private study, or personal, non-commercial research. Any re-use of the information contained within this document should be fully referenced, 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 to the owner(s) of the Intellectual Property Rights. |
| Divisions: | Schools > School of Science and Technology |
| Record created by: | Laura Borcherds |
| Date Added: | 08 Aug 2025 15:32 |
| Last Modified: | 08 Aug 2025 15:32 |
| URI: | https://irep.ntu.ac.uk/id/eprint/54153 |
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