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

畜牧业是繁殖和饲养牲畜的农业实践，是世界范围内主要的食品生产行业。这些动物的发育和生长不良、疾病、发病率和死亡率往往是由与肠道渗漏、肠道萎缩、感染和炎症相关的肠道健康状况不佳引起的，尤其是在动物幼年时。有必要采用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，特别是在饲料中抗生素的使用由于公众日益关注而变得越来越有限的情况下。肠道不仅是一个消化器官，也是一个化学感觉系统，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。包括钙敏感受体（CaSR）在内的味觉受体在动物的多种组织中表达，在营养感知和调节动物的生理和生长发育中起着非常重要的作用。我的研究计划的长期目标是研究正常生理或挑战性条件下动物肠道化学感应的分子机制以及营养吸收和肠道健康的调节。未来5年周期的短期目标是：(1)研究猪CaSR （pCaSR）在肠道中的分子分布和定位；(2)在肠内分泌细胞和肠细胞中鉴定潜在的pCaSR配体和与CaSR激活相关的细胞信号通路；(3)利用体外和体内方法阐明已鉴定的pCaSR配体在营养吸收和屏障功能中的作用。这项开创性研究的结果将有助于理解味觉受体（如CaSR）在肠道营养感知中的作用，并有助于开发CaSR调节剂，以改善断奶或其他具有挑战性条件下猪的吸收、屏障功能和肠道发育。所提出的研究将有助于改善动物肠道健康，提高营养物质利用效率，最大限度地降低细菌感染的风险，减少加拿大农业对抗生素的依赖，从而提高省和加拿大猪肉产业的竞争力。总体而言，这项假设驱动的研究将促进培养1名博士，2名硕士和3名本科生。我的高素质人才（HQP）将接受一个培训项目，该项目强调研究和专业技能的平衡获取，这将促进他们未来在学术界和私营企业的职业发展。

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.