Controlling enteric pathogens of poultry: Host/microbiota interactions, risk assessment and effective management interventions

据预测，未来25年全球人口将增加三分之一，其中发展中国家占97%。“到2050年可持续地养活90亿人”的能力是印度和英国政府的当务之急，印度的第十二个五年计划要求农业部门以每年4%的速度增长，以实现粮食安全。家禽养殖是生产供人类消费的动物蛋白的一种高效和具有成本效益的系统，但传染病的传播会损害肠道健康，并通过人畜共患病的传播对农场经济、动物福利和偶尔的人类健康产生重大影响。在英国和印度，最受关注的家禽胃肠道感染是由禽致病性大肠杆菌（APEC）、空肠弯曲杆菌、产气荚膜梭菌、艾美耳虫和沙门氏菌引起的。肠道定植易感性和感染结果直接受到许多因素的影响，包括宿主基因型、免疫状态、感染年龄、感染微生物菌株、共生肠道微生物群的组成以及其他急性或慢性感染的存在。宿主和微生物生物学、遗传学、表观遗传学、环境和农业实践之间存在着重要的相互作用。饮食的改变、疫苗或抗菌剂的使用以及“变薄”等群体干预措施可对肠道健康和致病微生物的进化和传播产生深远影响，并可能因宿主和微生物种群的遗传变异而放大。虽然在商业家禽品系的基因组学和基因分型方面取得的重大进展正在促进与易感性或耐药性相关的基因座的鉴定，但宿主和病原体多样性对疾病和生产结果的影响在很大程度上仍未得到探索。印度本土家禽品种具有丰富的遗传多样性，印度商业生产中经常使用的杂交外来品种与英国饲养的大多数家禽不同。农场一级胃肠道感染的流行和动态直接影响到个体农民的经济风险，并有助于全球对粮食安全和食品安全的总体关注。当前知识的差距引出了四个基本问题，这是本提案的框架：1。在英国和印度的家禽生产系统中，特定胃肠道感染和合并感染的流行病学是什么？宿主基因型是否对(a)特定微生物的流行、进化和传播以及(b)群体水平肠道微生物群的组成产生影响？印度和英国家禽生产中特定微生物种群的遗传变异水平是多少？哪些农场因素会影响肠道定植和特定微生物携带的风险？家禽饲养和管理实践的变化如何减轻这种风险？该提案汇集了英国和印度在家禽遗传学、动物卫生、流行病学、病理学和病原体生物学方面的专家。将采用一种多学科方法，结合宏基因组测序、基于高密度单核苷酸多态性的QTL制图、细菌学、寄生虫学、分子流行病学和数学建模，量化和预测农场和国家一级的疾病风险，并为制定干预和管理战略提供信息，包括未来的育种和畜牧业规划。

The global human population is predicted to increase by a third over the next 25 years, with countries of the developing world hosting 97% of this expansion. The ability to 'feed 9Bn people sustainably by 2050' is an urgent priority Indian and UK governments with the 12th Indian Five Year Plan requiring growth of the agricultural sector at 4% per annum to achieve food security. Poultry farming is a highly efficient and cost-effective system for producing animal protein for human consumption, but circulating infectious diseases compromise gut health and impact dramatically on farm economics, animal welfare and occasionally human health through transmission of zoonoses. Poultry gastrointestinal infections of most concern in UK and India are caused by avian pathogenic Escherichia coli (APEC), Campylobacter jejuni, Clostridium perfringens, Eimeria and Salmonella. Susceptibility to gut colonisation and the outcomes of infection are directly influenced by many factors including host genotype, immune status, age at infection, strain of infecting microbe, composition of commensal enteric microbiota and presence of other acute or chronic infections. There are significant interactions between host and microbe biology, genetics, epigenetics, the environment and farm practices. Changes to diet, use of vaccines or antimicrobials, and flock-level interventions such as 'thinning', can have profound effects on intestinal health and the evolution and spread of disease-causing microbes and may be amplified by genetic variation in host and microbe populations. Whilst major advances in genomics and genotyping of commercial poultry lines is facilitating the identification of loci linked to susceptibility or resistance, the impact of host and pathogen diversity on disease and production outcomes remains largely unexplored.There is rich genetic diversity in India's native poultry breeds, and the hybrid exotic lines often used in Indian commercial production are distinct from the majority of poultry reared in the UK. The prevalence and dynamics of gastrointestinal infection at farm-level has a direct bearing on economic risk to individual farmers and contributes to overall global concerns of food security and food safety.Gaps in current knowledge prompt four fundamental questions around which this proposal is framed: 1. What is the epidemiology of specified gastrointestinal infections, and co-infections, across UK and Indian poultry production systems?2. Does host genotype exert an influence on (a) the prevalence, evolution and transmission of specified microbes and (b) the composition of flock-level enteric microbiota?3. What is the level of genetic variation within specific microbial populations in Indian and UK poultry production?4. What on-farm factors affect the risk of enteric colonisation and carriage of specified microbes and how can changes in poultry husbandry and management practices mitigate this risk?The proposal brings together UK and India experts in poultry genetics, animal health, epidemiology, pathology and pathogen biology. A multidisciplinary approach combining metagenomic sequencing, high density SNP-based QTL mapping, bacteriology, parasitology, molecular epidemiology and mathematical modelling will be used to quantify and predict disease risks at farm and national levels and to inform the development of intervention and management strategies, including future breeding and husbandry planning.