Deciphering the role of host-pathogen-microbiome interactions in the development of bovine digital dermatitis

解读宿主-病原体-微生物组相互作用在牛指皮炎发展中的作用

• 批准号: 2599436
• 金额: --
• 依托单位: University of Liverpool
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2599436
• 关键词: Deciphering; role; host; pathogen; microbiome

Digital dermatitis (DD) is a painful, infectious, foot skin disease affecting ruminants worldwide. The disease is endemic on more than 90% of UK dairy farms and more than 50% of UK dairy cows are affected annually. In addition to pain and compromised animal welfare, DD is also associated with reduced milk yield, feed intake, and reproductive performance, and estimated to cost the UK dairy industry more than £74 million per year. Bacteria of the genus Treponema are considered the main pathogen associated with DD; however, the aetiopathogenesis and transmission patterns of the disease have not yet been elucidated. Current control strategies are generic and lack a substantial evidence base, relying on the empirical use of topical antibiotics and footbathing solutions containing heavy metals, such as copper sulphate, or formalin (carcinogen). We propose here to conduct a multidisciplinary, integrated study that will allow us to elucidate the role of host-pathogen-microbiome interactions in the development of DD, and advance our understanding of the disease's epidemiology, thereby offering tools to prevent the disease. More specifically we will:1. Confirm existing and identify new genomic markers (SNPs) and genomic regions that are associated with resistance to DD and develop breeding values for this trait utilising a unique existing database.2. Characterise the foot skin microbial communities (microbiome) before and during development of DD in a population of animals of known genetic propensity for resistance to DD and identify features of the microbiome associated with susceptibility to DD. We will deliver the first longitudinal, in depth characterisation of the foot skin microbiome in healthy animals and in animals with different DD infection patterns and of known genetic merit for resistance to DD. This will lead to a better understanding of the influence of the microbiome on host susceptibility to DD and has the potential to identify probiotic candidates; host genetic and management effects on the bovine foot skin microbiome will also be described.3. Investigate the role of host-pathogen-microbiome interactions in the development of DD lesions and identify infection reservoirs. We will quantify pathogen burden and identify main infection reservoirs. We will also identify differences in pathogen burden, and skin integrity between animals of different genetic merit for resistance to DD and between animals with different DD infection patterns.Mounting welfare and cost issues brought about by increasing prevalence of DD in bovine populations both nationally and worldwide demonstrate the timeliness of the proposed project.

指趾皮炎 (DD) 是一种影响全世界反刍动物的疼痛性传染性足部皮肤病。该疾病在英国超过 90% 的奶牛场流行，每年超过 50% 的英国奶牛受到影响。除了疼痛和动物福利受损之外，DD 还与产奶量、采食量和繁殖性能下降有关，估计每年给英国乳制品行业造成超过 7400 万英镑的损失。密螺旋体属细菌被认为是与 DD 相关的主要病原体；然而，该疾病的发病机制和传播模式尚未阐明。目前的控制策略是通用的，缺乏实质性的证据基础，依赖于局部抗生素和含有重金属（如硫酸铜或福尔马林）（致癌物）的足浴溶液的经验使用。我们在此建议进行一项多学科综合研究，使我们能够阐明宿主-病原体-微生物组相互作用在 DD 发展中的作用，并增进我们对该疾病流行病学的了解，从而提供预防该疾病的工具。更具体地说，我们将：1。确认现有并识别与 DD 抗性相关的新基因组标记 (SNP) 和基因组区域，并利用现有的独特数据库开发该性状的育种值。2．在已知具有 DD 抗性遗传倾向的动物群体中，描述 DD 发生之前和期间的足部皮肤微生物群落（微生物组）特征，并确定与 DD 易感性相关的微生物组特征。我们将首次对健康动物和具有不同 DD 感染模式且具有已知的 DD 抵抗遗传价值的动物的足部皮肤微生物组进行纵向、深入的表征。这将有助于更好地了解微生物组对宿主 DD 易感性的影响，并有可能确定候选益生菌；还将描述宿主遗传和管理对牛足皮肤微生物组的影响。3．研究宿主-病原体-微生物组相互作用在 DD 病变发展中的作用并确定感染库。我们将量化病原体负担并确定主要感染源。我们还将确定具有不同 DD 抵抗遗传价值的动物之间以及具有不同 DD 感染模式的动物之间病原体负担和皮肤完整性的差异。国内和世界范围内牛群中 DD 患病率不断增加所带来的福利和成本问题日益增加，这证明了拟议项目的及时性。