Abstract
The gut microbiome has been identified as an important regulator of host health, however, the effects of lifestyle factors such as physical activity and diet on this complex community are not yet fully understood. A substantial body of evidence has identified that diet has a profound impact on gut microbiome diversity and composition, however, much of this is from observational studies and rodent models and there are many research questions that remain to be investigated in human randomised controlled trials (RCTs). The effects of free sugar intake and the balance between total carbohydrate and total fat intake on the human gut microbiome are of particular importance to public health and require further study.A great many review articles have recently been published that focus on the effects of physical activity and exercise on the gut microbiome, with some strongly suggesting that exercise can beneficially modulate microbiome taxonomic composition and function. Despite the substantial research interest only a few RCTs have investigated the effects of exercise on the human gut microbiome. Their methods and results are also highly heterogenous with factors such as changes in body mass potentially confounding the findings. Beyond the assessment of the microbes present in the gut, little evidence is available regarding the concentrations of short-chain fatty acids in faeces and particularly in the peripheral circulation. These key metabolites serve as both a source of energy and as signalling molecules that purportedly mediate many of the effects that the gut microbiome exerts on host metabolism.
To provide a more comprehensive assessment of the interactions between lifestyle factors, the gut microbiome and host metabolism, it is important to assess the systemic concentrations of these metabolites and also to measure the expression of their receptors in metabolically-important tissues such as adipose and skeletal muscle. Therefore, the aims of this thesis were to investigate the effects of diet, exercise, and weight-loss on the gut microbiome across a series of RCTs, and also to assess the effects short-chain fatty acids on adipose tissue insulin sensitivity.
In Chapter 2 and Chapter 4, the effect of exercise was examined in the presence and absence of weight-loss, respectively. The effect of exercise independent of diet change on the gut microbiome was found to be minimal across relatively short training periods, and no changes were observed in short-chain fatty acid concentrations in faeces or fasting serum, nor in the expression of short-chain fatty acid receptors in adipose and skeletal muscle.
In Chapter 5, various concentrations of acetate, propionate and butyrate had no significant effect on unstimulated or insulin-stimulated glucose uptake in differentiated 3T3-L1 adipocytes.
In Chapter 3, the responses of the gut microbiome to three diet patterns were investigated. A moderate and a low intake of free sugar intake did not significantly affect the gut microbiome. In contrast, restricting total carbohydrate to levels that induce nutritional ketogenesis caused a significant shift in beta diversity and significantly reduced populations of probiotic bacteria including Bifidobacterium.
Despite the significant impact on gut microbiome composition, levels of short-chain fatty acids in fasting plasma were unaffected which suggests that changes in gut microbiome composition are not necessarily reflected in circulating concentrations of short-chain fatty acids.
| Date of Award | 28 Jun 2023 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Dylan Thompson (Supervisor), Francoise Koumanov (Supervisor), James Betts (Supervisor) & Javier Gonzalez (Supervisor) |