Biophysical defence in the mammalian gut: Unlocking the molecular mechanisms of dietary fibre interaction with mucin glycoproteins.

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Public Health England dietary recommendation for fibre is 30 g/day - twice above the average adult consumption in the UK. The recommendation is based on epidemiological evidence in which beneficial health outcomes, such as decreased risks of developing diabetes, heart disease and arthritis, are found to be associated with the diet rich in naturally integrated dietary fibre associated with the consumption of whole cereals, vegetables and fruit [SACN Carbohydrates and Health Report (2015)]. The definition of dietary fibre - "a type of carbohydrate that cannot be digested by our bodies' enzymes" - is based on chemical analysis and does not provide a fair prediction of its physiological effects. To date, there are no reliable measures of fibre "goodness" in term of its impact on the overall digestive health. This is partly due to a lack of understanding of fundamental mechanisms of how fibre "works" in human body.In this project, we aim to advance our understanding about the role of dietary fibre in the protection of the gut and its mucus lining. Mucus secretions play a vital role in maintaining gut health by forming a physical barrier and supporting healthy gut microbiota. In the healthy gut, microbes reside in the upper layers of the mucus film, and thus are kept separate from the intestinal tissues. This physical separation minimises the possibility of microbes' incursion into the epithelium, which can cause inflammatory response and possibility of developing a chronic condition or gut dysfunction.The mucus role in digestion and drug delivery is often overlooked due to mucus chemical complexity and heterogeneity. We take a different approach and put our focus on mucus biophysical properties such as flow properties (viscosity), "sliminess" (viscoelasticity) and lubrication. The project will consider and explore the role of these biophysical factors in order to identify the mechanisms by which dietary fibre affects barrier and protective functionality of mucus to ensure our digestive organs remain in good working order, especially in aging population. Taking full advantage of novel characterisation and imaging facilities, the proposed study will consider a systematic approach whereby research will progress from model dietary fibre systems to food fibre particles isolated form white wheat flour. We will seek to vary systematically the dietary fibre composition, particles size and its mechanical property. The latter is of particular importance for advancing the area of minimally processed foods, which must strive to retain the natural structure of dietary fibre where the "soft" components (soluble fibre) are integrated within the solid-like particles (insoluble fibre). Further, through enzymatic modification and physical processing, we seek to develop dietary fibre assemblies that specifically designed to interact with mucus. In particular, we will focus on processing of wheat endosperm cell walls, a key fibre component of white wheat flour, to target the delivery of fibre functionality through one of the key cereal crops. The outcomes of this study will advance the knowledge base of how functional dietary fibre can benefit mucus integrity and its barrier function. In practice, the results of this study will provide scientific underpinning and a set of new measurement techniques and tools for the food industry to enable rational development of healthier foods in an effort to increase the fibre intake across the UK. The insights generated will also guide the development of improved crops with enhanced dietary fibre functionality. The broader impact of this study has the potential to guide emerging research that targets major problems and challenges of digestive health such as gluten intolerance, inflammatory bowel dysfunctions and cystic fibrosis.