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Title: Inter-individual variability of polyphenol metabolism and colonic health
Author: Alkhaldy, Areej
ISNI:       0000 0004 5355 3653
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 2014
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Abstract:
It has been proposed that polyphenol-rich foods have a role in disease prevention and are associated with health benefits due to their antioxidant, anti-inflammatory, prebiotic, and antibacterial properties. However, associated health benefits depend on their intake, metabolism, and bioavailability. The metabolism and the bioavailability of polyphenols have been studied in young adults and show substantial variability. As the majority of polyphenols are metabolised in the colon, this may result in different bioactive microbial metabolites in the large intestine where they may have an impact on the risk of colorectal cancer (CRC). This variability could be due to: 1) dietary habits including intake polyphenol-rich foods; 2) ethnic-specific colonic microbiota; and 3) ageing and its effect on colonic physiology. Little is known about the impact of ethnicity, ageing, and the risk of CRC on polyphenol metabolism. Therefore, this thesis aimed to investigate the effect of the factors that could have an impact on the colonic metabolism of dietary polyphenols in a human feeding study measuring the biomarkers of polyphenol metabolism, colonic fermentation, and gut health; and an in-vitro faecal fermentation study measuring the colonic metabolites of quercetin-3-O-rutinoside (rutin). The first aim of this thesis (Chapter 3) was to examine the effect of ethnicity (Europeans versus Indians) on polyphenol metabolism. The findings of this study suggest that ethnicity could have a role on the colonic metabolism of polyphenols which could be due to the differences in disease incidence between countries such as the lowest risk of CRC in India among the world. The Indian group excreted less urinary phenolic acid after the high-polyphenol diet compared to the Europeans; however, Indians were more capable and faster in metabolizing rutin in the in-vitro model. This could be due to the differences in: 1. Genetics and its effect on gastrointestinal tract absorption. 2. Gut microbiota, as Indians have a significantly higher level of Bifidobacterium. 3. Gut environment, in particular the colonic pH and SCFA could have an influence as the colonic pH was lower in the Indian group. 4. Cultural daily diet between groups, as Indians significantly consumed a high amount of onions, tomatoes, chillies, spices, curry-based products, and yoghurt. These food types are high in polyphenols, fibre, and probiotics. The second study of this thesis aimed to investigate the effect of ageing on polyphenol metabolism. The results suggest another factor, ageing, which could influence the colonic metabolism of polyphenols. The older group excreted less urinary phenolic acid and some of the acid was not detected in certain of the participants’ urine compared to the younger group. However, the sum of the phenolic acid that formed after the faecal fermentation of rutin was not significantly different between the groups. This could suggest different reasons behind these variations. First, the lack of absorption of some phenolic acids by the older group as ageing was shown to decrease the colonic absorption. Secondly, the effect of ageing on gut microbiota composition and function. Thirdly, changes in dietary habits and physical activity may be influenced by ageing. Thus, this may suggest that older people can have fewer benefits of polyphenol metabolites which could be associated with an increase in risk for age-related diseases including CRC. As the risk of CRC is different between countries and increases with age, the supportive findings of the first and second study suggest that ethnicity and ageing could have a role on the metabolism of polyphenols so this raises the questions whether a low intake of polyphenols can be one of the factors that may lead to CRC, or whether polyphenols can reduce the risk of CRC due to their colonic health benefits. Therefore, the last study examined the metabolism of polyphenols on patients who are at risk of CRC (history of polyps). No significant differences were observed between the healthy control and polypectomy groups in terms of the sum urinary phenolic acid excretion and phenolic acid formation in the faecal fluids. However, some phenolic acids were not detected in all of the urine samples of the polypectomy group as well as one acid in the faecal fermentation fluids, while some of the acids were not detected in few participants in the healthy group. No hard conclusion can be made from this study due to the small sample size. However, this study gives us an idea that there could be differences if a larger sample size were used. Therefore, more studies are needed to determine the effect of CRC risk as being one of the factors that can influence the metabolism of polyphenols. In conclusion, the work of this thesis showed that ethnicity, ageing, and gut health are likely some of the key factors that could contribute to the variations in polyphenol metabolism which were observed previously by many in-vivo and in-vitro studies. These variations could result in bioavailability variation and consequential differences in the biological activity of polyphenol metabolites leading to differences in health and optimal health among individuals.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.631063  DOI: Not available
Keywords: QH301 Biology ; QH345 Biochemistry ; QP Physiology ; RZ Other systems of medicine
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