Gut chemosensing and the regulation of nutrient absorption and barrier function in pigs

猪肠道化学传感以及营养吸收和屏障功能的调节

• 批准号: RGPIN-2017-04967
• 负责人: Yang, Chengbo
• 金额: $ 3.79万
• 依托单位: University of Manitoba
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=743580
• 关键词: Gut; chemosensing; regulation; nutrient; absorption

Animal husbandry is the agricultural practice of breeding and raising livestock, and it is a major food-producing industry worldwide. Poor development and growth, disease, morbidity and mortality of these animals are often caused by poor gut health associated with leaky gut, intestinal atrophy, infection and inflammation, particularly when the animals are young. There is a need for better solutions that can be practised to improve gut health for sustainable animal production, especially when antibiotic use in feed has been becoming more limited due to mounting public concerns. The gut is not only a digestive organ but also a chemosensory system that mediates the orchestration of physiological and metabolic responses required to maintain homeostasis in animals through cellular and molecular signaling cascades within the gut and among the gut, brain and other organs. Taste receptors including calcium sensor receptor (CaSR) are expressed in various tissues of animals, play very important roles in nutrient sensing and regulate the physiology, growth and development of the animals. The long-term goal of my research program is to investigate the molecular mechanisms of gut chemosensing and the regulation of nutrient absorption and gut health in animals under normal physiological or challenging conditions. The short term objectives of the next five year cycle are to: (1) investigate the molecular distribution and localization of porcine CaSR (pCaSR) in intestine; (2) identify the potential ligands of pCaSR and cell signaling pathways related to CaSR activation in enteroendocrine cells and potentially in enterocytes; and (3) elucidate the roles of identified pCaSR ligands on nutrient absorption and barrier functions using in vitro and in vivo approaches. The results of this seminal research will contribute to the understanding of the roles of taste receptors (e.g. CaSR) in intestinal nutrient sensing and to the development of CaSR modulators for improving absorption, barrier function and gut development during weaning or other challenging conditions in pigs. The proposed studies will lead to improving animal gut health, improving nutrient utilization efficiency, minimizing the risk of bacterial infection and reducing our dependence on antibiotics in Canadian agriculture, thereby contributing to the competiveness of the provincial and Canadian pork industry. Collectively, this hypothesis-driven research will promote to the training of 1 PhD, 2 MSc and 3 undergraduate students. My highly qualified personnel (HQP) will be exposed to a training program that emphasizes a balanced acquisition of research and professional skills, which will enhance their future career development in both academia and private industry.

畜牧业是饲养牲畜的农业实践，是世界范围内的主要食品生产行业。这些动物的不良发育和生长、疾病、发病率和死亡率通常是由与肠漏、肠萎缩、感染和炎症相关的不良肠道健康引起的，特别是当动物年幼时。需要更好的解决方案来改善肠道健康，以实现可持续的动物生产，特别是当抗生素在饲料中的使用由于公众日益关注而变得越来越有限时。肠道不仅是一个消化器官，也是一个化学感受系统，通过肠道内以及肠道、大脑和其他器官之间的细胞和分子信号级联，介导维持动物体内稳态所需的生理和代谢反应的协调。味觉受体包括钙感受器受体（CaSR）在动物的多种组织中均有表达，在营养感受和调节动物的生理、生长发育等方面发挥着重要作用。我的研究计划的长期目标是研究肠道化学传感的分子机制，以及在正常生理或挑战性条件下动物营养吸收和肠道健康的调节。未来5年的短期目标是：（1）研究猪CaSR（pCaSR）在肠道中的分子分布和定位;（2）鉴定pCaSR的潜在配体和与肠内分泌细胞和肠上皮细胞中CaSR活化相关的细胞信号通路;以及（3）使用体外和体内方法阐明鉴定的pCaSR配体对营养吸收和屏障功能的作用。这项开创性研究的结果将有助于理解味觉受体（例如CaSR）在肠道营养感测中的作用，并有助于开发CaSR调节剂，以改善断奶或其他挑战性条件下猪的吸收，屏障功能和肠道发育。拟议的研究将改善动物肠道健康，提高营养利用效率，最大限度地减少细菌感染的风险，并减少我们对加拿大农业抗生素的依赖，从而有助于提高该省和加拿大猪肉行业的竞争力。总的来说，这项假设驱动的研究将促进1个博士，2个硕士和3个本科生的培训。我的高素质人员（HQP）将接受培训计划，该计划强调研究和专业技能的平衡获取，这将增强他们未来在学术界和私营行业的职业发展。