RoboHog: developing an in vitro gut model system of the porcine hindgut

RoboHog：开发猪后肠的体外肠道模型系统

• 批准号: NC/X002160/1
• 负责人: Anthony Buckley
• 金额: $ 25.78万
• 依托单位: University of Leeds
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=NC%2FX002160%2F1
• 关键词: RoboHog; developing; vitro; gut; model

Just like humans, pigs host a wide variety of microbes that inhabit the body and are essential for host health. The microbial communities (collectively known as the microbiota) that reside in the digestive tract play a vital role in metabolising food to provide essential nutrients, protecting against pathogens, and maintaining the wellbeing of the digestive tract. Careful selection of feed and supplements can maximise the beneficial effects of the gut microbiota for sustainable livestock performance, improved wellbeing, lowering feed costs, and reducing environmental impact. Studies to identify optimum feed conditions largely takes place in the animals themselves, which limits the scope and size of these studies. If we were able to carry out laboratory based studies this would allow a much broader set of experiments to be carried out, without the ethical concerns associated with using animals in this way. Working with the National Pig Centre and key industrial partners, we will demonstrate the potential for such an approach through "RoboHog - a Pig Gut Model". The model itself draws inspiration from a high-throughput "Human Gut Model" that we have been developing for the past 4 years which allows similar studies to be carried out for better understanding the human gut composition and infection treatment. This transfer of technology is feasible due to the many similarities between the human and pig gut. "RoboHog" itself consists of 3 zones, each with a different set of conditions that are controlled to represent the pig gut. The first zone is fed with a mimic of feed, products from this trickle into the second and then the third zone - each region develops its own distinct microbial population, just as a large intestine would within a pig. We will demonstrate the power of RoboHog through two studies. The first study will consider the impact of supplements and nutrient regimes on the health benefits conferred by the microbiota. We will feed RoboHog different feed compositions and monitor microbial populations and other indicators of nutritional benefit. This study will run in parallel to one taking place using pigs at the National Pig Centre so that we can learn how to relate findings in one to another. The second study will demonstrate how the model can capture the impact of pathogens on the gut health and to test therapies against these pathogens. We will challenge the gut model with a pathogen, such as Salmonella, and show how microbes can be manipulated to affect disease outcome. This could then be used as a model to research how bio-therapeutics could be used to influence pig health. Throughout the project, we will work with industry partners to ensure the relevance of our studies and to explore how such technologies can be used more widely to support sustainable farming practices. We will run knowledge transfer events to showcase both the technology and the findings and, by working with the University of Leeds Research Innovations Services, we will establish ways for researchers/industry to access this technology allowing them to run their own studies. This will reduce the dependency on using animals in feed trials and pathogen investigations, whilst offering greater flexibility in establishing more sustainable farming practices.

就像人类一样，猪身上也有各种各样的微生物，这些微生物对宿主的健康至关重要。驻留在消化道中的微生物群落（统称为微生物群）在代谢食物以提供必需的营养素，抵御病原体和维持消化道的健康方面发挥着至关重要的作用。仔细选择饲料和补充剂可以最大限度地发挥肠道微生物群的有益作用，以实现可持续的牲畜性能，改善健康状况，降低饲料成本并减少对环境的影响。确定最佳饲养条件的研究主要发生在动物本身，这限制了这些研究的范围和规模。如果我们能够进行基于实验室的研究，这将允许进行更广泛的实验，而没有与以这种方式使用动物相关的伦理问题。我们将与国家养猪中心和主要的工业合作伙伴合作，通过“RoboHog -猪肠模型”展示这种方法的潜力。该模型本身的灵感来自于我们在过去4年中一直在开发的高通量“人类肠道模型”，该模型允许进行类似的研究，以更好地了解人类肠道组成和感染治疗。由于人类和猪肠之间有许多相似之处，这种技术转让是可行的。“RoboHog”本身由3个区域组成，每个区域都有一组不同的条件，这些条件被控制来代表猪肠。第一个区域用模拟饲料喂养，产品从这个涓涓细流进入第二个区域，然后是第三个区域-每个区域都发展出自己独特的微生物种群，就像猪体内的大肠一样。我们将通过两项研究来展示RoboHog的强大功能。第一项研究将考虑补充剂和营养方案对微生物群所带来的健康益处的影响。我们将为RoboHog提供不同的饲料成分，并监测微生物种群和其他营养效益指标。这项研究将与在国家养猪中心使用猪进行的一项研究平行进行，以便我们能够学习如何将一项研究结果与另一项研究结果联系起来。第二项研究将展示该模型如何捕捉病原体对肠道健康的影响，并测试针对这些病原体的疗法。我们将用病原体（如沙门氏菌）挑战肠道模型，并展示如何操纵微生物来影响疾病结果。然后，这可以作为一个模型，研究生物疗法如何用于影响猪的健康。在整个项目中，我们将与行业合作伙伴合作，以确保我们的研究的相关性，并探索如何更广泛地使用这些技术来支持可持续农业实践。我们将举办知识转移活动，展示技术和研究成果，并通过与利兹大学研究创新服务部合作，为研究人员/行业建立访问该技术的方法，使他们能够进行自己的研究。这将减少在饲料试验和病原体调查中对动物的依赖，同时在建立更可持续的农业实践方面提供更大的灵活性。