Assessing the bioactivity of immune-related microRNAs in colostrum and milk from high and low immune responder cows on human intestinal epithelial cells

牛乳是一种极好的蛋白质来源，具有很高的生物学价值和抗微生物活性，有助于预防传染病。牛初乳和牛奶中这些具有生物活性的宿主防御相关蛋白的存在和浓度是由遗传控制的，近年来，与被称为microRNAs(MiRNAs)的小RNA分子有关。到目前为止，一些研究表明，在奶牛的初乳和牛奶中发现了大量的miRNAs。有趣的是，免疫相关的miRNAs在牛乳中大量表达，特别是在初乳中，表明它们对乳腺的免疫功能以及新生牛犊和人类的肠道发育和免疫具有重要的免疫调节作用。这些牛研究的另一个有趣的观察是，总miRNAs和已鉴定的单个miRNAs有相当大的差异。确定的总miRNAs和单个miRNAs的差异与实验设计的差异和所研究奶牛的背景有关。随着Guelph大学获得专利的高免疫应答(HIR)技术的发展，我们认为将高免疫应答奶牛的初乳和牛奶miRNAs的转录组与低免疫应答奶牛的miRNAs进行比较，这将是一种新颖的方法。此外，免疫相关miRNAs在牛初乳和牛奶中的表达谱以及它们对人类肠道发育和免疫的生物学意义仍有待阐明。本研究的主要目的是研究miRNAs在高、低免疫反应奶牛初乳和乳中的表达谱，确定其遗传力，以及它们对牛和人肠道上皮细胞的调节功能。拟议的研究结果将为免疫相关miRNAs在高免疫反应性奶牛的初乳和牛奶中的免疫调节作用提供新的见解，并强调牛奶的健康益处。特别是，这项研究有望为牛初乳和牛奶mRNAs的创新应用打开大门，从而为加拿大农业食品行业、消费者和学术机构带来短期和长期的好处。

Bovine milk is an excellent source of proteins of high biological value and antimicrobial activity that contribute to protection against infectious diseases. The presence and concentration of those bioactive host defence-related proteins in bovine colostrum and milk is controlled by genetics and in recent years, is related to small RNA molecules known as microRNAs (miRNAs). So far, a few studies have shown that miRNAs are found in large amounts in cow's colostrum and milk. Interestingly, immune-related miRNAs were abundantly expressed in cow's milk especially colostrum suggesting their crucial immune-regulatory effect on immune function of the mammary gland and the gut development and immunity of newborn calf as well as humans. Another interesting observation with these bovine studies was the considerable variation in total miRNAs and the identified individual miRNAs. Differences in total and individual miRNAs identified were related to the differences in experimental design and the background of cows whose milk was studied. With development of the University of Guelph patented High Immune Response (HIR) technology; we thought it would be novel to evaluate the transcriptome of colostrum and milk miRNAs from high immune responder cows in comparison to those from low immune responders. In addition, the expression profiles of immune-related miRNAs in bovine colostrum and milk and their biological significance on human gut development and immunity remain to be elucidated. The main focus of the proposed research is to characterize the expression profile of miRNAs in high and low immune responding cows' colostrum and milk, determine their heritability, and their regulatory function on bovine and human intestinal epithelial cells. The results of the proposed study should provide new insight into the immunoregulatory role of immune-related miRNAs in colostrum and milk from high immune responder cows with emphasis on the health benefit of milk. In particular, this study is expected to open door for innovative applications of bovine colostrum and milk mRNAs, leading to short- and long-term benefits to the Canadian agri-food industry, consumers as well as the academic institution