Are microbiomes important to mammary gland health in dairy cows?

乳房炎是乳房(乳腺)的细菌感染。每年约有50%的奶牛患有乳房炎，其中约四分之一死亡或被扑杀。它是导致奶牛患病和死亡的最常见原因。乳房炎的管理是通过良好的卫生以及通过乳头给药的抗生素来治疗和/或预防。超过150种细菌可以引起乳房炎，其中5种细菌类型被认为是导致大多数病例的细菌类型。目前的研究和管理集中在单个菌株上，其想法是了解和开发针对每种菌株的疫苗和治疗方法将导致更好地控制乳房炎。到目前为止，这种方法并没有减少乳房炎的发生，乳房炎仍然是奶牛和其他哺乳期农场动物的一种非常常见的疾病。当奶牛在产犊前6-8周(干乳期)停止挤奶时，通常会给奶牛注射抗生素，以清除现有的感染。具有讽刺意味的是，有很好的证据表明，已经被某些细菌种类定植的乳房最不可能患乳腺炎。在这些乳房中，细菌几乎不会引起炎症，也不会降低牛奶的质量。我们还不知道是什么导致奶牛从乳房中携带低水平的表面无害的细菌并且没有患病，然后发展为乳房炎。我们现在知道，许多种类的细菌共同生活(一个群落)在动物身体的许多位置发现，包括肠道，口腔，最近，人类和奶牛的乳腺。在肠道中，当平衡的细菌群落被扰乱，使一种细菌菌株占优势时，就可能发生疾病，例如引起腹泻。在这笔赠款中，我们假设奶牛乳房中存在一个自然的细菌群落，该群落在奶牛首次由小牛哺乳之前就已经存在，并且这个群落在预防乳腺炎方面发挥了重要作用。我们的目标是：1.研究何时可以在小牛犊和小母牛的乳房中首次检测到细菌。2.研究乳房中细菌的变化，从奶牛在干乳期开始时使用抗生素，一直到下一头小牛出生，以及接下来的四周，这段时间是奶牛最有可能患乳房炎的时期。新技术使我们有可能检测和识别牛奶样本中存在的所有细菌种类，而不必培养它们。我们将从2个牧场的200头奶牛的乳房中抽取乳样12次，从晾干到产犊后4周，共提供800个乳房样本。我们将选择至少65个发生乳房炎的季度样本集和65个没有发生乳房炎的季度样本集，并使用现代分子工具来鉴定这些奶牛季度中的所有细菌，并调查微生物群落在干燥、产犊、挤奶、乳房炎和使用抗生素治疗时如何形成和随时间变化，以及如果不受疾病和治疗的干扰，微生物群落是否保持稳定。我们将使用统计分析来确定特定的细菌或细菌组合是否有助于预防乳房炎，抗生素如何影响疾病的管理和控制，并为开发和维持奶牛健康以及牛奶产量和质量的新战略提供想法。

Mastitis is a bacterial infection of the udder (mammary gland). Each year ~ 50% of cows suffer from mastitis and about 1 in 4 of these die or are culled. It is the most common cause of disease and death in dairy cows. Mastitis is managed by good hygiene along with treatment and/or prevention by antibiotics administered via the teat. Over 150 types of bacteria can cause mastitis with 5 bacterial types believed to cause most cases.Research and management is currently focused on individual strains with the idea that understanding and developing vaccines and treatments for each strain will lead to better control of mastitis. To date such an approach has not led to a reduction in the occurrence of mastitis and mastitis remains a very common disease in dairy cows and other lactating farm animals. Antibiotics are given routinely when a cow stops milking 6-8 weeks before calving (the dry period) to clear existing infection. Ironically, there is good evidence that udders that are already colonised by certain bacterial species are the least likely to suffer from mastitis. In these udders the bacteria present cause very little inflammation and do not reduce milk quality. We do not yet understand what happens that leads to cows changing from carrying low levels of apparently harmless bacteria in its udder and suffering no disease to then going on to develop mastitis.We now know that many species of bacteria living together (a community) are found in many sites of an animal's body, including the gut, mouth and, most recently, both human and cow mammary glands. In the gut it appears that disease can occur when the balanced bacterial community is disturbed allowing one bacterial strain to dominate, e.g. causing diarrhoea. In this grant we hypothesise that there is a natural community of bacteria in the cow udder that is present before the cow is first suckled by its calf and that this community plays an important part in preventing mastitis. We aim to:1. Investigate when bacteria can first be detected in the udders of young calves and heifers. 2. Investigate how the bacteria in the udder change over time from when a cow is treated with antibiotics at the beginning of the dry period through to the birth of its next calf and for the following 4 weeks, the period when cows are most likely to get mastitis. New technologies have made it possible for us to detect and identify all the bacterial species present in a milk sample without having to grow them. We will take milk samples from the mammary gland quarters of 200 cows from 2 farms on 12 occasions from drying off to 4 weeks after calving to give 800 mammary gland quarter sample sets in total. We will select at least 65 quarter sample sets where mastitis occurred and 65 sets where it did not and use modern molecular tools to identify all the bacteria in these cows' quarters and investigate how the microbial community forms and changes over time at drying off, with calving, milking, mastitis, and treatment with antibiotics and whether it remains stable if not disturbed by disease and treatment. We will use statistical analysis to determine whether specific bacteria or combinations of bacteria help protect against mastitis, how antibiotics affect the management and control of the disease and produce ideas for new strategies to develop and maintain cow health and milk output and quality.