Rational microbial-based interventions against enteric disease in young livestock

由于免疫功能有限和微生物群落不发达，幼畜特别容易感染传染病。微生物群落是一种微生物生态系统，在包括肠道在内的一系列身体部位定居，并抑制病原微生物的定居。在过去，高水平的抗生素被用来控制这种感染。然而，抗菌素耐药性的出现导致了对此类使用的更严格控制，需要能够在生命早期预防或减少接种疫苗困难的感染的替代品。一种这样的方法是通过使用益生菌等活的微生物干预措施来调节微生物群，以提供更强的抗感染能力。根据定义，益生菌是“活的微生物，当给予足够的量时，会给宿主带来健康益处”。虽然益生菌在兽医实践中的使用越来越多，但识别和应用益生菌培养的方法主要是经验的，对其功能所依据的任何机制的了解有限。该项目的目的是确定选定的益生菌菌株，并了解和澄清它们在预防和治疗牛犊和仔猪腹泻的常见细菌原因方面的有益作用。特别是对大肠杆菌和肠沙门氏菌感染产生的影响，这两种感染是新生儿或断奶后腹泻的最常见原因，通常是致命的。该项目将使用基于测序的方法来分析患病动物和健康动物的肠道微生物群，以确定哪些细菌物种与“健康”的肠道有关，并选择这些细菌作为潜在的益生菌。此外，我们将开发基于牛和猪肠道细胞的2-D和3-D感染模型，使我们能够在细胞和分子水平上使用包括成像、微生物学和转录分析在内的一系列方法来确定宿主、病原体和微生物组之间的相互作用。成功的候选人将加入一个跨学科的团队，并将提供一系列学科的培训，包括微生物学、细胞培养、病理学、免疫学、成像和显微镜。微生物组测序将在基因组学和微生物组的基本生物信息学分析方面发展技能。该项目将设在布里斯托尔的朗福德校区，最近的招聘正在那里发展一个充满活力的年轻社区，研究感染、免疫和抗菌素耐药性。将有机会与国内和国际合作伙伴合作，并在行业内进行安置。

Young livestock are particularly susceptible to infectious disease due both to limited immune function and poorly developed microbiomes, the ecosystem of microbes that colonise a range of body sites including the gut and act to inhibit colonisation by pathogenic microbes. In the past high levels of antibiotics were used to control such infections. However, the emergence of antimicrobial resistance has led to tighter control of such use, and alternatives that can prevent or reduce infection early in life where vaccination is difficult are needed. One such approach is to modulate the microbiome to offer greater resistance to infection through the use of live microbial interventions like probiotics. Probiotics are, by definition, "live microorganisms that, when administered in adequate amounts, confer a health benefit on the host". Although probiotics are increasingly used in veterinary practice, the approaches to identify and apply probiotic cultures are largely empirical with limited understanding of any mechanisms that underlie their function. The aim of the project is to identify selected strains of probiotics and understand and clarify their beneficial role in preventing and treating common bacterial causes of diarrhoea in calves and piglets. In particular, the effects produced against Escherichia coli and Salmonella enterica infection which are amongst the most frequent causes of, often fatal, neonatal or post weaning diarrheoa. The project will use sequencing-based approaches to analyse the intestinal microbiomes of diseased verses healthy animals to determine which bacterial species are associated with a 'healthy' gut and select these as potential probiotics. Alongside this we will develop 2-D and 3-D bovine and porcine intestinal cell-based infection models that will allow us to determine host:pathogen:microbiome interactions at a cellular and molecular level using a range of approaches including imaging, microbiological and transcriptional analysis as the project develops. The successful candidate will join an interdisciplinary team and will offer training in a range of disciplines including microbiology, cell culture, pathology, immunology, imaging and microscopy. The microbiome sequencing will develop skills in genomics and basic bioinformatic analysis of the microbiome. The project will be based at Bristol's Langford Campus where recent recruitment is developing a vibrant, young community of research in infection, immunity and antimicrobial resistance. Opportunity will be made to work with national and international collaborators and to undertake placement within industry.