Are microbiomes important to mammary gland health in dairy cows?

乳腺炎是乳房（乳腺）的细菌感染。每年约有50%的奶牛患有乳腺炎，其中约有1/4的奶牛死亡或被淘汰。它是奶牛疾病和死亡的最常见原因。乳腺炎通过良好的卫生沿着通过乳头施用抗生素的治疗和/或预防来管理。超过150种细菌可以引起乳腺炎，其中5种细菌被认为是引起大多数病例的原因。目前研究和管理的重点是单个菌株，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腺炎。到目前为止，这种方法还没有导致乳腺炎的发生率降低，并且乳腺炎仍然是奶牛和其他泌乳农场动物中非常常见的疾病。当奶牛在产犊前6-8周（干奶期）停止挤奶时，常规给予抗生素，以清除现有的感染。具有讽刺意味的是，有充分的证据表明，已经被某些细菌物种定殖的乳房最不可能患乳腺炎。在这些乳房中，存在的细菌几乎不会引起炎症，也不会降低牛奶质量。我们还不知道是什么原因导致奶牛从乳房中携带低水平的看似无害的细菌，并没有患病，然后发展为乳腺炎。我们现在知道，在动物身体的许多部位，包括肠道，口腔，以及最近发现的人类和奶牛乳腺中，发现了许多种细菌共同生活（一个社区）。在肠道中，当平衡的细菌群落被扰乱，允许一种细菌菌株占主导地位时，似乎会发生疾病，例如引起腹泻。在这项研究中，我们假设在奶牛第一次被小牛哺乳之前，奶牛乳房中存在一个天然的细菌群落，并且这个群落在预防乳腺炎中起着重要作用。我们的目标是：1.调查何时可以在小牛和小母牛的乳房中首次检测到细菌。2.研究从奶牛在干奶期开始时接受抗生素治疗到下一头小牛出生以及接下来的4周（奶牛最有可能患乳腺炎的时期），乳房中的细菌如何随时间变化。新技术使我们能够检测和识别牛奶样品中存在的所有细菌种类，而无需培养它们。我们将从2个农场的200头奶牛的乳腺乳区从干乳期至产犊后4周共采集12次乳汁样本，共计800个乳腺乳区样本集。我们将选择至少65个发生乳腺炎的乳区样本集和65个未发生乳腺炎的乳区样本集，并使用现代分子工具鉴定这些奶牛乳区中的所有细菌，并研究干乳期、产犊期、挤奶期、乳腺炎期和抗生素治疗期微生物群落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细菌或细菌组合是否有助于预防乳腺炎，抗生素如何影响疾病的管理和控制，并为发展和保持奶牛健康以及牛奶产量和质量的新策略提供思路。

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.