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

就像人类一样，猪体内有各种各样的微生物，这些微生物对宿主的健康至关重要。消化道内的微生物群落（统称为微生物群）在代谢食物、提供必需营养、抵御病原体和维持消化道健康方面发挥着至关重要的作用。精心选择饲料和补充物可以最大限度地发挥肠道微生物群对可持续牲畜生产性能、改善健康、降低饲料成本和减少环境影响的有益作用。确定最佳饲料条件的研究主要是在动物身上进行的，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，而不用担心以这种方式使用动物所带来的伦理问题。与国家养猪中心和主要工业伙伴合作，我们将通过“机器猪-猪肠道模型”展示这种方法的潜力。该模型本身从我们过去4年一直在开发的高通量“人类肠道模型”中获得灵感，该模型允许进行类似的研究，以更好地了解人类肠道成分和感染治疗。由于人类和猪的肠道有许多相似之处，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，这些条件被控制以代表猪的肠道。第一个区域用模拟饲料喂养，从这个区域流出的产品进入第二个区域，然后是第三个区域——每个区域都有自己独特的微生物种群，就像猪的大肠一样。我们将通过两项研究来展示RoboHog的力量。第一项研究将考虑补充剂和营养制度对微生物群所带来的健康益处的影响。我们将给RoboHog饲喂不同的饲料组合，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进行的一项用猪进行的研究同时进行，这样我们就可以了解如何将研究结果相互联系起来。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治疗方法。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。这可以作为一个模型来研究生物疗法如何影响猪的健康。在整个项目中，我们将与行业合作伙伴合作，确保我们研究的相关性，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，展示技术和发现，通过与利兹大学研究创新服务中心合作，我们将为研究人员/行业建立获取这项技术的途径，使他们能够开展自己的研究。这将减少对在饲料试验和病原体调查中使用动物的依赖，同时在建立更可持续的农业实践方面提供更大的灵活性。

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.