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

数字皮炎(DD)是一种痛苦的、传染性的足部皮肤病，影响着全世界的反刍动物。这种疾病在英国90%以上的奶牛场流行，每年有超过50%的英国奶牛受到影响。除了疼痛和动物福利受损外，DD还与牛奶产量、饲料摄入量和繁殖性能下降有关，据估计，英国乳制品行业每年损失超过7400万GB。密螺旋体属细菌被认为是引起该病的主要病原体，然而，该病的病因和传播方式尚未阐明。目前的控制策略是通用的，缺乏实质性的证据基础，依赖于经验上使用局部抗生素和含有重金属的足浴溶液，如硫酸铜或福尔马林(致癌物质)。我们建议进行一项多学科的综合研究，以阐明宿主-病原体-微生物组相互作用在DD发生发展中的作用，并增进我们对该病流行病学的理解，从而为预防该病提供工具。更具体地说，我们将：1.确认和确定与抗病相关的新的基因组标记(SNP)和基因组区域，并利用现有的唯一数据库开发该性状的育种价值。在对DD有已知遗传倾向的动物种群中，确定在DD发生之前和期间的足部皮肤微生物群落(微生物群)的特征，并确定与DD易感性相关的微生物群的特征。我们将首次对健康动物和具有不同DD感染模式的动物的足部皮肤微生物群进行纵向、深入的表征，这些动物对DD具有已知的遗传优势。这将有助于更好地了解微生物群对宿主对DD易感性的影响，并有可能确定候选益生菌；还将描述宿主对牛脚皮肤微生物群的遗传和管理效应。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，并确定主要的感染源。我们还将确定不同抵抗DD基因的动物之间在病原体负担和皮肤完整性方面的差异，以及具有不同DD感染模式的动物之间的差异。由于DD在全国和全球牛群中的流行率不断上升，带来的福利和成本问题证明了拟议计划的及时性。

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.