Caecal Microbiome Transplant:a novel approach to Campylobacter control and improving broiler chicken gut heath.

The modern broiler (or meat-producing) chicken is one of the best examples of how the appliance of science and selective breeding can lead to an efficient and sustainable system to produce cheap and nutritious food. However this comes at a cost. The modern hybrid broiler breed has a number of health and welfare problems including poor gut health than can lead to a problem known as 'wet litter' due to watery faeces. In turn birds stand on the wet litter leading to skin burns and irritation that affect their welfare. Several types of bacteria that can cause food poisoning can also live and replicate in the intestines of broiler chickens and can be shed in the faeces leading to rapid spread of these bacteria, including Campylobacter and Salmonella, though chicken flocks and on to the human food chain. Understanding how the chicken keeps its intestines healthy and how it interacts both with disease-causing bacteria and the bacteria that naturally occur in the gut (the microbiota) are important in improving welfare of these animals and in finding ways we can control the disease-causing bacteria or pathogens.

In recent years the importance of the gut microbiome in heath and disease has become increasingly apparent, not just on the health of the gut but on areas as diverse as obesity and mental health. One area of this research with a particularly strong profile is in Faecal Microbiota Transplant also called more simply a faecal or stool transplant. As it suggests this involves transfer faecal material from a health donor to patients with the hospital-acquired infection, Clostridium difficle. The approach has been very successful and has been applied experimental to other intestinal diseases and even to conditions affecting the nervous system.

In this project we propose to transfer the healthy microbiome from older chickens to newly hatched chicks. In modern chicken production chicks have no contact with their mothers, the main source of the microbiome in mammals. As such they do not develop a 'chicken' microbiome until later in life. We believe this contributes both to the poor gut health of broiler chickens and to their susceptibility to Campylobacter infection. We have shown in initial experiments that transfer of the intestinal (caecal) content from an 8-week old healthy bird improves the gut health of the chicks but more significantly both reduces the levels of Campylobacter in the chicken gut in experimental infection and hinders this bacteria spreading from bird-to bird. We believe that this can be developed as an effective control for Campylobacter.
In the project we aim to do the following
1. Understanding how the transplant modifies the microbiota and affects the immune system
2. Show which changes to the microbiome and immune system are important in reducing susceptibility to infection
3. Further develop the transplant technology and assess if methods used to deliver live vaccines to chicks can be adopted to deliver a transplant

In this project we propose develop the caecal microbiome transplant sufficiently to attract industrial partners to take forward to becoming a product that can help improving the health of billions of chickens reared annually in the world and reduce the levels of Campylobacter which cause over half a million cases of gastroenteritis in England and Wales each year.

The role of the intestinal microbiome in health and disease has become increasingly prominent. Maintenance of a 'healthy' microbiome is central to gut health and approaches ranging from pre and probiotics to human faecal microbiome transplants are utilised in maintaining or restoring gut health. The chicken is no exception to this and the use of probiotics and competitive exclusion products is well-established in the poultry industry to promote gut health and productivity and reduce the carriage of foodborne bacterial pathogens. However, the efficacy of single species probiotics or undefined, cultured microflora preparations is mixed and the approaches to development have largely been empirical in nature. Broiler chicken production in particular suffers from problems associated with poor gut health and high levels of Campylobacter jejuni.
We present preliminary data that shows early transplantation of a complete caecal microbiome to newly hatched broiler chicks promotes gut health and significantly reduces susceptibility to Campylobacter and reduces transmission within a group. We hypothesise that commercial chicks do not develop a natural 'chicken microbiome' early in life and that by transplant of such a microbiome early in life we can improve gut and mucosal immune development. In this proposal we aim to understand and characterise how a caecal microbiome transplant affects gut development, changes the structure of the intestinal microbiome through series of in vivo experiments coupled to immunological and histological analysis of the gut along with 16S metagenomic analysis to determine the microbiome changes. We will determine if enhanced immunological development, competitive exclusion effects or a combination of these underlies increased resistance to Campylobacter. Finally we will determine factorss such as age of transplantation on these effects and seek to utilise vaccine technologies to deliver a microbiome effectively to chicks in large numbers.

Who will benefit from this research?
Poultry Producers and retailers
The public
Health Services
Animal Welfare groups
Academia and pharma

How will they benefit?

The proposed work will have two main benefits:
1. A substantial reduction in carriage of Campylobacter in poultry.
2. Improvement to gut health and welfare of broiler chickens

The Poultry Industry:
Both main benefits impact directly in improving the sustainability and welfare conditions in broiler chicken production. Healthier birds are in general more productive and require less use of antimicrobials and in turn reduce the likelihood of development of antimicrobial resistance and potential drug residues within meat and the environment. Reducing Campylobacter in chicken production will in turn reduce its entry into the food chain thereby providing a considerable reduction in the half-a-million or more estimated human cases in the UK each year.

The Public:
Reducing Campylobacter levels in chicken has a considerable public health benefit. Over half a million people are affected by campylobacteriosis each year in the UK. Whilst most cases this is self-limiting diarrhoea, between 10-20% of cases present to their GP and a smaller number develop invasive disease leading to an estimated 50-100 deaths each year and many more cases where serious sequelae such as Guillain-Barre syndrome develop. If, as our data suggests, that a caecal micro biome transplant can reduce caecal levels by more than 2Log10 then reductions in human cases associated with poultry of the order 60-90% should follow. This would more than halve current levels.This in turn reduces the burden on the health service in treatment and in days work or education lost to illness.

Improvements to animal welfare are also desired by the public and this should help deliver improvements to gut health in broilers.

Health Service:
With between 50-70,000 conformed cases of campylobacteriosis in England and Wales each year, a reduction of the levels we would propose, has the potential to reduce the need for diagnostics and treatment in primary care of around 30,000 presenting cases each year along with the health benefits to the majority of milder cases who do not present to their GP.

Animal Welfare Groups:
Improving gut health directly and through reduction of pathogen carriage will improve the welfare of broiler chickens. This is desirable to a range of pressure groups.

Academia and Pharma:
The findings in this proposal will underpin the development of new microbiota based prophylactics for use in poultry as well as improve our understanding of the role of the microbiome in gut and immune development that will also underpin vaccine development and well as inform future studies of the chicken gut and its pathogens.