RoboHog: developing an in vitro gut model system of the porcine hindgut
Lead Research Organisation:
University of Leeds
Department Name: School of Food Science and Nutrition
Abstract
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.
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.
Technical Summary
The gut microbiota are important determinants of pig health. Largely residing in the hindgut, it fermentatively digests nutrients contributing to host energy needs and, when in eubiotic status, it also prevents colonisation by pathogens. Current methods to study pig gut microbiota either entail sacrifice of animals for direct sampling from the gut, or indirect faecal sampling. Batch-culture fermentation models of the pig gut do not attempt to model the regional nuances in the microbiota composition and, being a closed system, precludes the time necessary for microbiota adaptation and stabilisation. This limits their value for studying the microbiota and their responses to interventions.
'RoboHog - A Pig Gut Model' builds on our recent work in establishing a small scale, clinically representative 'Human Gut Model'. This is a continuous culture fermentation model designed to capture regional variations in microbiota composition. This has been successfully employed to study microbiota responses in human clinical and nutritional trials.
To adapt and demonstrate the applicability of such a model, the temporal and spatial nutritional, physiochemical and microbiological regional variations in the porcine hindgut will be characterised and conditions set within RoboHog accordingly. A parallel study with an industry-funded pig nutrition trial at the National Pig Centre will test the validity of RoboHog by comparative analysis. In addition, a challenge study will demonstrate the power of RoboHog to study the impact and treatment of microbial pathogens, such as Salmonella, on hindgut eubiosis.
Working closely with industrial partners and our Research Innovation Service will ensure the knowledge exchange and capacity building necessary to adopt RoboHog as the standard for preliminary microbiota intervention studies. RoboHog complies fully with the principles of the 3Rs. It will facilitate development of treatments to improve pig health and performance.
'RoboHog - A Pig Gut Model' builds on our recent work in establishing a small scale, clinically representative 'Human Gut Model'. This is a continuous culture fermentation model designed to capture regional variations in microbiota composition. This has been successfully employed to study microbiota responses in human clinical and nutritional trials.
To adapt and demonstrate the applicability of such a model, the temporal and spatial nutritional, physiochemical and microbiological regional variations in the porcine hindgut will be characterised and conditions set within RoboHog accordingly. A parallel study with an industry-funded pig nutrition trial at the National Pig Centre will test the validity of RoboHog by comparative analysis. In addition, a challenge study will demonstrate the power of RoboHog to study the impact and treatment of microbial pathogens, such as Salmonella, on hindgut eubiosis.
Working closely with industrial partners and our Research Innovation Service will ensure the knowledge exchange and capacity building necessary to adopt RoboHog as the standard for preliminary microbiota intervention studies. RoboHog complies fully with the principles of the 3Rs. It will facilitate development of treatments to improve pig health and performance.
