- Title
- Interactions between taste genetics, diet and the gastrointestinal microbiota; consequences for metabolism
- Creator
- Turner, Alexandria
- Resource Type
- thesis
- Date
- 2021
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- Taste is one of the five fundamental senses. Gustatory taste is responsible for the detection of essential nutrients and for the avoidance of potential toxins. G-protein coupled receptors (GPCRs) detect three of the five taste modalities (sweet, umami and bitter). In humans, these include three type 1 taste receptors (T1Rs) that heterodimerise to detect sweet and umami tastants, and over 25 type 2 taste receptors (T2Rs) capable of detecting hundreds of different bitter compounds. These receptors are particularly important in the detection of energy sources (carbohydrates and proteins), as well as potentially toxic bitter substances. Oral taste receptors modulate taste sensitivities, preferences, and therefore, dietary intakes. However, more recently, G-protein coupled taste receptors (T1Rs and T2Rs; collectively referred to as TRs throughout this thesis) have also been identified throughout the body, including throughout the respiratory and gastrointestinal (GI) systems. There is emerging evidence to suggest that some TRs have extra-oral roles in modulating the secretion of metabolic hormones. The hormones modulated by TRs are involved in regulating processes such as appetite, glucose homeostasis, gut motility and lipid metabolism. In this way, altered receptor expression and the presence of functional single nucleotide polymorphisms (SNPs) may be involved in modulating risk for metabolic conditions such as obesity and type 2 diabetes, not only by altering dietary intakes, but also via actions on metabolic hormone secretion. However, the existing body of evidence regarding these associations is limited in both the number and scope of studies. Furthermore, TRs may have non-gustatory roles in the detection of bacterial components and modulation of immune responses. This has been demonstrated in the respiratory tract, where multiple sweet and bitter TRs are expressed. Given that TRs can detect bacteria in the oral cavity and respiratory tract, it is possible that intestinal TRs may similarly interact with the intestinal microbiota. The composition of the gut microbiome is strongly related to risk for, and presence of, metabolic conditions like obesity and insulin dysregulation. These are the same conditions thought to be associated with altered taste receptor expression and functional variance in taste genetics. Therefore, there may be an association between GI TRs and the microbiome with consequences for metabolic dysfunction. To examine these potential relationships, a mixed-methods approach was designed to capitalise on available resources. These included existing antibiotic mouse models and a cell model to investigate potential relationships between intestinal bacteria and taste receptor expression, as well as a well-characterised, elderly Australian cohort (n = 563) to examine the effects of certain SNPs on metabolic dysfunction over the lifetime. To investigate these associations, existing antibiotic mouse models were used to examine the effects of antibiotic-induced dysbiosis on the expression levels of 15 different taste genes throughout the GI tract (Chapter 2). Of the genes assessed, most were found to be expressed in GI tissues. Furthermore, the expression levels of some genes were significantly modulated in response to antibiotics compared to control mice. Overall, the results suggest that intestinal dysbiosis may modulate the expression of TRs throughout the GI tract. However, the mechanisms of this potential interaction were still unknown. To elucidate the mechanisms behind the potential interaction between TRs and intestinal bacteria a subsequent study was undertaken using an enteroendocrine cell model. STC-1 cells were exposed to multiple types and concentrations of bacterial metabolites. Short-chain fatty acids (SCFAs) are major bacterial metabolites known to interact with other GPCRs throughout the body. It was determined that four taste genes were highly expressed in these cells. Importantly, the expression of some of these taste genes were modulated in response to certain types and concentrations of SCFAs. Additionally, it was determined that 48h SCFA exposure significantly reduced the secretion of GLP-1 (glucagon-like peptide-1; a metabolic hormone involved in glucose regulation and satiety). Overall, the results from this study support an interaction between intestinal TRs and bacteria, and suggest potential consequences for metabolic hormone regulation. To build on the ideas presented in previous chapters, existing blood samples and dietary and health data from a large cross-sectional study were leveraged for secondary analyses (Chapters 4 and 5). Participants were genotyped, the association of the presence or absence of eight common SNPs across different taste genes were assessed against a variety of metabolic markers/conditions. These genotypes were also assessed for relationships with dietary intake of certain foods. Overall, it was determined that the presence of some taste SNPs were associated with conditions like BMI, obesity and dyslipidaemia. Importantly, these associations appeared to be largely independent of estimated dietary intakes of certain highrisk foods. Together, these results suggest that the presence of certain SNPs may be associated with metabolic dysfunction, and that these associations may relate to the extra-oral functions of TRs. The results presented in this thesis extend our currently limited understanding of the roles of TRs throughout the body. Together, these studies suggest that a previously unexplored relationship may exist between intestinal bacteria and oral and extra-oral TRs. Overall, this thesis lays the necessary foundations for further research into the mechanisms of this potential relationship and the consequences for multiple metabolic health outcomes. This may have future implications for the development of therapies to combat the increasing rates of obesity and obesity-associated metabolic conditions.
- Subject
- taste genetics; diet; gastriontestinal microbioa; metabolism
- Identifier
- http://hdl.handle.net/1959.13/1489130
- Identifier
- uon:52623
- Rights
- Copyright 2021 Alexandria Turner
- Language
- eng
- Full Text
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