Intensive milk feeding in neonatal calves: Investigations on the development of the intestinal adaptive immune system and the intestinal microbiota and their interaction

新生犊牛强化喂奶：肠道适应性免疫系统和肠道微生物群的发育及其相互作用的研究

• 批准号: 531414549
• 负责人: Dr. Wendy Liermann
• 金额: --
• 依托单位: Institut für Ernährungsphysiologie "Oskar Kellner"
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/531414549?language=en
• 关键词: Intensive; milk; feeding; neonatal; calves

The reduction of calf losses continues to be a major challenge. One of the main causes of calf losses is diarrhoea. Especially the postnatal period is critical for pre-weaning mortality due to diarrhoea. The high incidence in this period results from the low degree of maturity of the neonatal immune repertoire which is prone to inadequately reactions against essential nutrients or insufficient defence against pathogens. Because of the steady cross-talk between the intestinal immune system and the commensals the generation of the intestinal microbiota plays a key role in the establishment of tolerance and defence. However, currently specific mechanisms of the interactions between the intestinal immune system and the microbiota are not fully understood. Previous studies dealing with parenteral feeding or undernutrition show that the nutrients are a crucial stimulus for the establishment of a proper immune system and a beneficial microbial community in the intestine. In practice restrictive pre-weaning milk or milk replacer (MR) feeding is common. With regard to the fact that the nutritional level of this feeding regime is unable to exploit the growth potential of the calves it is also thinkable that a restrictive feeding regime in the neonatal period may impede the establishment of the intestinal immune system and the microbiota due to a low degree of nutritional stimulation. In contrast, an increase of this stimulation by ad libitum milk feeding could support this establishment. With regard to these hypotheses a feeding trial will be conducted with 40 calves fed either restrictively or ad libitum with a high-quality MR. The study will focus on the general animal condition and health. The growth performance of the animals will be documented. Faeces will be analyzed with regard to their physical, chemical and microbiological state. Blood samples will be collected to determine clinical and immunological traits. The animals will be slaughtered on day 8 and day 29 after birth, respectively. During slaughtering especially intestinal tissues and contents will be collected. The T and B cell specific immune response of the calves will be measured by flow cytometry and gene expression analyses. Sequencing analyses will be used to characterize the intestinal microbiota. The investigations allow analyses of the interactions between the microbiota and the T and B cell based immune response especially by studying the short chain fatty acid receptor, FFAR2 expression, on the intestinal immune cells. The focus of the project is the investigation of the poorly explored establishment of the intestinal immune system and the microbiota as well as their interaction in neonatal calves and the feeding regimes as a potential impact factor on this establishment. Therefore, beside the basic research this project contributes to the adjustment of feeding regimes of neonatal calves to their requirements and the reduction of diarrhoeal diseases in the pre-weaning period.

减少小牛损失仍然是一项重大挑战。腹泻是导致犊牛减少的主要原因之一。尤其是出生后阶段对腹泻导致的断奶前死亡率至关重要。这一时期的高发病率是由于新生儿免疫系统的成熟度较低，容易对基本营养物质反应不足或对病原体的防御不足。由于肠道免疫系统和共生体之间稳定的相互作用，肠道微生物区系的产生在建立耐受性和防御机制中起着关键作用。然而，目前对肠道免疫系统和微生物区系之间相互作用的具体机制还不完全清楚。以前关于肠外喂养或营养不良的研究表明，营养物质是建立适当的免疫系统和肠道内有益微生物群落的关键刺激因素。在实践中，严格的断奶前哺乳或代乳粉(MR)喂养是很常见的。关于这种喂养制度的营养水平不能开发小牛犊的生长潜力这一事实，也可以认为，在新生期实行限制喂养制度可能会由于营养刺激程度较低而阻碍肠道免疫系统和微生物区系的建立。相比之下，通过随意喂奶来增加这种刺激可以支持这种建立。关于这些假设，将对40头犊牛进行饲养试验，无论是限制饲喂还是自由饲喂，并配备高质量的公牛。该研究将集中在一般动物状况和健康方面。动物的生长表现将被记录下来。将分析粪便的物理、化学和微生物状态。将采集血样以确定临床和免疫学特征。这些动物将分别在出生后第8天和第29天被屠宰。屠宰期间，特别是肠道组织和内容物将被收集。将通过流式细胞仪和基因表达分析来测量小牛的T和B细胞特异性免疫反应。测序分析将用于描述肠道微生物区系的特征。这些研究可以分析微生物区系与基于T和B细胞的免疫反应之间的相互作用，特别是通过研究肠道免疫细胞上的短链脂肪酸受体FFAR2的表达。该项目的重点是调查探索不足的肠道免疫系统和微生物区系的建立及其在新生牛犊中的相互作用，以及喂养制度作为建立这种建立的潜在影响因素的情况。因此，除了基础研究外，该项目还有助于调整初生犊牛的饲养方式，以满足其需要，并减少断奶前腹泻疾病的发生。