The gut microbiota as a novel nutritional target to influence systemic inflammation associated with prevalent health disorders

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Lad, N., 2023. The gut microbiota as a novel nutritional target to influence systemic inflammation associated with prevalent health disorders. PhD, Nottingham Trent University.

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Abstract

Systemic inflammation is an underlying symptom present in many diseases including Asthma and Obesity. This inflammation may arise internally with the release of pro inflammatory adipokines such as asprosin, or through increased gut permeability which allows endotoxin, derived from gram-negative bacteria, to cross into the bloodstream and mediate an innate immune inflammatory response. Both asprosin and endotoxin are elevated in conditions of metabolic disease, which share a similar inflammatory profile with Asthma. Currently, Asthma treatments relieve symptoms rather than targeting the trigger that causes the inflammation. Therefore, to target the source of the inflammation, the use of internally derived anti-inflammatory agents, such as short chain fatty acids (SCFAs) may provide a therapeutic answer. SCFAs are produced from the metabolism of dietary substrates (e.g. prebiotics) by the gut microbiota, which appear to provide anti-inflammatory health benefits systemically as well as locally.

Therefore, a series of studies addressed the role of SCFAs (acetate, butyrate, and propionate) on endotoxin- and asprosin-induced inflammation in models of Asthma and Obesity using human bronchial epithelial cells and human white adipocyte cells to assess their impact on metabolism. Molecular techniques including Western blot and RT-qPCR, and mitochondrial dynamic analysis were explored to examine metabolism. Furthermore, a human invention trial was conducted to evaluate the use of prebiotics to improve inflammation, lung function, and Asthma symptoms in participants.

The outcomes of these in vitro studies suggest that SCFAs have the capacity to mitigate endotoxin and asprosin induced inflammation in airway and adipocyte cells. Whilst in vivo studies, where participants with Asthma were given a prebiotic supplementation, showed improvements in serum metabolic markers in. Taken together, these data suggest that increasing SCFA production through dietary interventions may provide a novel management tool to relieve cellular inflammatory damage in patients with Asthma or Obesity-related Asthma to potentially relieve Asthma symptoms over time.

Item Type:	Thesis
Creators:	Lad, N.
Date:	January 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:	23 Aug 2023 08:45
Last Modified:	23 Aug 2023 08:45
URI:	https://irep.ntu.ac.uk/id/eprint/49602