Title: Digestion and Fermentation in the Lower GI Tract
Funder: Biotechnology and Biological Sciences Research Council

Abstract: There has been much research on the colonic microbiota in the last decade. The major thrust of this research has been comparative studies between different population groups based upon 16S profiling of the microbiota from stool samples, and associated studies seeking functional analyses of human microbiota within mouse models. Human faecal samples are also commonly used to â€˜seedâ€™ in vitro colonic models to investigate metabolic derivatives of foods. These studies have provided evidence for the physiological role that gut microbiota play in the fermentation of food entering the colon as well as the multiple means by which resident intestinal bacteria provide immunological, metabolic and neurological benefits to the host, and contribute to well-being. However, the translation of studies from mouse and in vitro models, based upon faecal samples, which may not represent the resident bacteria at the site of fermentation in vivo, to normal digestive processes in humans is open to challenge. From birth, host and dietary carbohydrates are the main drivers influencing gut bacteria composition. A low-fibre diet characteristic of industrialized countries has long been hypothesized to contribute to â€˜Westernâ€™ diseases such as inflammatory bowel disease. Enabling an effective communication between the gut microbiota and the host via the provision of microbiota-accessible carbohydrates adapted to the physiological state of the host is paramount to optimise human health throughout life. Many phytochemicals are present in plant foods as glycosides or other conjugates which can be hydrolysed and metabolised by gut bacteria, and influence the growth of beneficial bacteria, exerting prebiotic-like effects. For example, supplementing the diets of experimental animals or human subjects with polyphenol-rich foods or extracts has been reported to increase the prevalence of commensal bacteria groups, such as Bifidobacteria and Lactobacilli, that generate significant quantities of potentially beneficial short chain fatty acids, and the decrease in the prevalence of bacterial groups considered potentially detrimental. However, there is little understanding of how polyphenols cause these pre-biotic like effects. It is also increasingly recognised that the intestinal microbiota play a critical role in the metabolism of polyphenols, glucosinolates and other sulphur containing phytochemicals and significantly affect the amount of ingested phytochemical derivatives. This theme will consider how the gut microbiota generate novel metabolites from macronutrients and phytochemicals that are delivered via the upper GI tract, and the mechanisms by which these metabolites may influence nutrient signalling, hormone release and satiety. Moreover, building upon our combined expertise in dietary carbohydrates and phytochemicals we propose to address the impact of the interaction between these plant-derived components on the GI microbiota composition and function, host barrier function and metabolism._x000D__x000D_ _x000D__x000D_ We will adopt approaches developed at Imperial College London to intubate and sample luminal and mucus associated microbiota from the ileum and ascending colon. We will explore how foods that differ in their chemical and physical composition (as developed in Theme 1, and used in studies in Theme 2) can result in acute and long-term changes in gut microbiota and the nature of fermentation. We have an emphasis on starch degrading microbiota, and how they modulate the fermentation of â€˜resistantâ€™ starch entering the colon, their influence on the chemical and biophysical properties of the gut mucosa and intestinal barrier function, and how they stimulate the differentiation and functioning of enteroendocrine L-cells. Additionally, we will quantify the biotransformation of dietary phytochemicals by the gut microbiota, and the effect of phytochemicals on gut microbiota diversity and metabolism. We have an emphasis on sulphur-containing phytochemicals and complex polyphenols.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: ORAL AND GASTROINTESTINAL