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

英国公共健康中心推荐的膳食纤维摄入量为每天30克--是英国成年人平均摄入量的两倍。这项建议是基于流行病学证据，在这些证据中，发现有益的健康结果，如降低患糖尿病、心脏病和关节炎的风险，与富含天然综合膳食纤维的饮食有关，并与食用全谷类、蔬菜和水果有关[SACN碳水化合物与健康报告(2015)]。膳食纤维的定义是“一种不能被人体酶消化的碳水化合物”，它的定义基于化学分析，并没有提供对其生理影响的公平预测。迄今为止，就纤维对整体消化健康的影响而言，还没有可靠的衡量纤维“好坏”的标准。这在一定程度上是因为缺乏对纤维如何在人体内发挥作用的基本机制的了解。在这个项目中，我们的目标是促进我们对膳食纤维在保护肠道及其粘液衬里中的作用的理解。粘液分泌物通过形成物理屏障和支持健康的肠道微生物群，在维持肠道健康方面发挥着至关重要的作用。在健康的肠道中，微生物居住在粘液膜的上层，因此与肠道组织保持分离。这种物理分离将微生物侵入上皮的可能性降至最低，从而导致炎症反应和发展为慢性病或肠道功能障碍的可能性。由于粘液化学的复杂性和异质性，粘液在消化和药物输送中的作用经常被忽视。我们采取了一种不同的方法，将重点放在粘液的生物物理特性上，如流动特性(粘度)、“粘滞性”(粘弹性)和润滑性。该项目将考虑和探索这些生物物理因素的作用，以确定膳食纤维影响粘液屏障和保护功能的机制，以确保我们的消化器官保持良好的工作状态，特别是在人口老龄化的情况下。充分利用新的表征和成像设备，拟议的研究将考虑一种系统的方法，通过这种方法，研究将从模型膳食纤维系统发展到从白小麦粉中分离出的食品纤维颗粒。我们将寻求系统地改变膳食纤维的组成、颗粒大小和机械性能。后者对于推进最低加工食品领域特别重要，必须努力保留膳食纤维的自然结构，在这种结构中，“软”成分(可溶性纤维)整合在类固体颗粒(不溶性纤维)中。此外，通过酶修饰和物理处理，我们寻求开发专门设计用于与粘液相互作用的膳食纤维组件。特别是，我们将专注于小麦胚乳细胞壁的加工，这是白色小麦面粉的关键纤维成分，目标是通过关键的谷类作物之一提供纤维功能。这项研究的结果将促进关于功能性膳食纤维如何有助于粘液完整性及其屏障功能的知识基础。在实践中，这项研究的结果将为食品行业提供科学依据和一套新的测量技术和工具，使其能够合理开发更健康的食品，努力增加英国各地的纤维摄入量。所产生的见解还将指导开发具有增强膳食纤维功能的改良作物。这项研究的更广泛影响有可能指导针对消化健康的主要问题和挑战的新兴研究，如面筋不耐受、炎症性肠道功能障碍和囊性纤维化。

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.