Development of immune function and avian gut health

Lead Research Organisation: University of Oxford
Department Name: Zoology

Abstract

Improving the health of animals reared for food is an essential element of sustainable farming and the DIFAGH programme is focussed on improving avian gut health. Poultry products (meat and eggs) represent the largest source of animal protein in the world and with increasing demand for efficient, sustainable supply with the highest ethical and ecological standards of farming. Prevention of disease is one of the most important factors in poultry welfare and sustainable production, especially since the majority of birds are young and immunologically immature (particularly in the gut). The DIFAGH project will directly impact on this area, focusing on the development of probiotic regimens that will improve the immune competence of young poultry and protect them against bacterial diseases. Improving immune competence will improve resistance of young birds to disease and improve the responses generated by vaccines. Improving gut health is a priority for the poultry industry since problems in the gut contribute significantly in other areas such as litter quality and the attendant issues related to hock burn and foot problems.The development of a strong consortium in the field of avian gut health will lead to a range of international exchange opportunities enriching the academic and cultural development of staff and students.

The DIFAGH project represents a trans-European consortium involving experts in avian immunology, infectious disease, microflora analysis and probiotic development. We will employ state of the art approaches to identify and test for the effectiveness of probiotic formulations to improve the gut health of chickens. Importantly we will also seek formulations that reduce the capacity for infections to establish within the gut of poultry (including those with zoonotic capability).

The benefits of our studies will positively impact on the welfare of many millions of poultry in the field. Furthermore, it will improve consumer protection by subsequently reducing the need for antimicrobial treatments, the prevalence of Campylobacter and Salmonella in poultry as well as reducing the incidence of disease in humans. All studies will be licensed by appropriate agencies and ethical review bodies with the highest standards of animal care.

Technical Summary

The DIFAGH proposal links cutting edge technologies with gut flora modification experiments to define
the contribution of microbial colonisation to the development of chicken immune capacity, resistance
and transmission of infection. The programme unites efforts of experienced avian immunologists,
pathogen specialists and gut flora microbiologists, forming a trans-EU team of scientists to address the
complex interactions between the chicken and its microbial environment. The proposed programme of
work will deliver a combination of high quality fundamental research and practical outcomes, defining a
new framework for selecting pro-biotic formulations to accelerate immune development, improve poultry
gut health and reduce pathogen carriage. Specifically, we will determine the effects of pro-biotic
formulations of differing complexity on the development of immune capability and the outcome of
infection. We will also determine the effects on colonisation, persistence and transmission of
Campylobacter and Salmonella.These analyses will be supported by in vitro and in vivo approaches to determine the microbial recognition events
within the bird (such as those mediated by the avian Pattern Recognition Receptor system) and the nature of the lymphocyte response (functional and repertoire based analyses). One important anticipated outcome of this work will be to develop a new set of selection criteria for
identifying components for a defined pro-biotic formulation.

Planned Impact

The impact of a trans-EU programme are expicitly stated in the original application (see attachment) and include both academic, translational and improved welfare of poultry farmed throughout Europe.

Publications

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Colles F (2016) Monitoring chicken flock behaviour provides early warning of infection by human pathogen Campylobacter in Proceedings of the Royal Society B: Biological Sciences

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Han Z (2016) The influence of age on Campylobacter jejuni infection in chicken in Developmental & Comparative Immunology

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McLoughlin K (2016) Host Selection of Microbiota via Differential Adhesion. in Cell host & microbe

 
Description This is part of a large pan-European consortium of researchers under the EMIDA umbrella with studies aimed at identifying the effects of microbiota on immune development and gut health. The work in this project has focussed on analysis of chickens raised in different environments including those with no microbiota (germ free) and with defined microbiota (gnotobiotic). We have also colonised some GF birds with single defined bacterial species to identify whether different components of the microbiota stimulate different responses in the chicken gut. The consortium includes experts from the UK, Germany, France, Czech Republic and Israel with 6 research groups undertaking different aspects of the programme. The UK element of the project is largely focussed on analysing the immune development and function of chickens raised in germ-free and/or gnotobiotic environments and comparing these with birds raised under conventional conditions. There is a tight relationship between the complexity of the microbiota and the complexity of the immune system in the gut and different components of the microbiota have different effects on gut immune development and function. We have also been able to identify that the immune system responds strongly to "commensal microbes" including responses associated with all arms of the immune system and specific IgA is raised against these commensal microbes. The overall aim of this work is to try and develop rational candidate microbes for inclusion in probiotics and to identify how many different microbes might be needed in such treatments.
Exploitation Route This project is providing key evidence for how different microbes interact with the host and how potential microbes may influence immune development. The work is focussed on chicken gut health and has real potential to impact on the development of defined probiotics for use in chickens. Moreover, this work moves towards the development of a framework for probiotic discovery with defined function(s) in terms of both host immune development and their potential to affect gut health. This framework would have impact in the poultry industry as well as in the broader arena of probiotic use including in humans or other animals.
Sectors Agriculture, Food and Drink,Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description We have been working with industrial partners to apply some of the approaches developed in the course of this project.
First Year Of Impact 2016
Sector Agriculture, Food and Drink
Impact Types Economic

 
Description ANIWHA
Amount £1,200,000 (GBP)
Funding ID BB/K001388/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 07/2016 
End 06/2019
 
Title Immune repertoire analyses (avian) 
Description We have developed systems for measuring the immune repertoire in chickens and use or are developing similar methodologies for use in a wide range of other species. 
Type Of Material Technology assay or reagent 
Year Produced 2014 
Provided To Others? Yes  
Impact A range of studies are underway. 
 
Title immune repertoire analyses (general) 
Description We have developed systems for measuring the immune repertoire in chickens, mice and humans, we are developing similar methodologies for use in a wide range of other species. 
Type Of Material Technology assay or reagent 
Year Produced 2014 
Provided To Others? Yes  
Impact Collaborations underway. 
 
Description DIFAGH 
Organisation French National Institute of Agricultural Research
Department Microbiology and the Food Chain
Country France 
Sector Public 
PI Contribution This project represents an EMIDA-ERANET programme linking a number of laboratories together. I lead the overall programme and all research teams including my own are working on a range of collaborative projects. We bring expertise in gut immunology, avian immunology, T/B cell repertoire analyses, innate immunity and infection biology to the consortium.
Collaborator Contribution All of the partners engage in cross-laboratory collaborations. The tasks are divided as follows: Immunity (Oxford and Munich), Germ-free chickens (Munich, Oxford and INRA), Campylobacter infections (Hannover), Salmonella infections (INRA), enterocyte biology (Jerusalem), microbiota biology (Lohmann), microbiome profiling and proteomics (Brno).
Impact A series of publications are currently being prepared, most of which involve multiple partners and can be considered multidisciplinary by brining together expertise across a range of areas including immunology, poultry health, infectious disease, microbiology and mathematical biology. One manuscript was recently published led by the Hannover group on the ability of different Campylobacter isolates (from humans and chickens) to colonise chickens and that these induced different immune responses in the chickens PMID 26827832.
Start Year 2011
 
Description DIFAGH 
Organisation Gottfried Wilhelm Leibniz Universität Hannover
Country Germany 
Sector Academic/University 
PI Contribution This project represents an EMIDA-ERANET programme linking a number of laboratories together. I lead the overall programme and all research teams including my own are working on a range of collaborative projects. We bring expertise in gut immunology, avian immunology, T/B cell repertoire analyses, innate immunity and infection biology to the consortium.
Collaborator Contribution All of the partners engage in cross-laboratory collaborations. The tasks are divided as follows: Immunity (Oxford and Munich), Germ-free chickens (Munich, Oxford and INRA), Campylobacter infections (Hannover), Salmonella infections (INRA), enterocyte biology (Jerusalem), microbiota biology (Lohmann), microbiome profiling and proteomics (Brno).
Impact A series of publications are currently being prepared, most of which involve multiple partners and can be considered multidisciplinary by brining together expertise across a range of areas including immunology, poultry health, infectious disease, microbiology and mathematical biology. One manuscript was recently published led by the Hannover group on the ability of different Campylobacter isolates (from humans and chickens) to colonise chickens and that these induced different immune responses in the chickens PMID 26827832.
Start Year 2011
 
Description DIFAGH 
Organisation Hebrew University of Jerusalem
Country Israel 
Sector Academic/University 
PI Contribution This project represents an EMIDA-ERANET programme linking a number of laboratories together. I lead the overall programme and all research teams including my own are working on a range of collaborative projects. We bring expertise in gut immunology, avian immunology, T/B cell repertoire analyses, innate immunity and infection biology to the consortium.
Collaborator Contribution All of the partners engage in cross-laboratory collaborations. The tasks are divided as follows: Immunity (Oxford and Munich), Germ-free chickens (Munich, Oxford and INRA), Campylobacter infections (Hannover), Salmonella infections (INRA), enterocyte biology (Jerusalem), microbiota biology (Lohmann), microbiome profiling and proteomics (Brno).
Impact A series of publications are currently being prepared, most of which involve multiple partners and can be considered multidisciplinary by brining together expertise across a range of areas including immunology, poultry health, infectious disease, microbiology and mathematical biology. One manuscript was recently published led by the Hannover group on the ability of different Campylobacter isolates (from humans and chickens) to colonise chickens and that these induced different immune responses in the chickens PMID 26827832.
Start Year 2011
 
Description DIFAGH 
Organisation Lohmann Animal Health
Country Germany 
Sector Private 
PI Contribution This project represents an EMIDA-ERANET programme linking a number of laboratories together. I lead the overall programme and all research teams including my own are working on a range of collaborative projects. We bring expertise in gut immunology, avian immunology, T/B cell repertoire analyses, innate immunity and infection biology to the consortium.
Collaborator Contribution All of the partners engage in cross-laboratory collaborations. The tasks are divided as follows: Immunity (Oxford and Munich), Germ-free chickens (Munich, Oxford and INRA), Campylobacter infections (Hannover), Salmonella infections (INRA), enterocyte biology (Jerusalem), microbiota biology (Lohmann), microbiome profiling and proteomics (Brno).
Impact A series of publications are currently being prepared, most of which involve multiple partners and can be considered multidisciplinary by brining together expertise across a range of areas including immunology, poultry health, infectious disease, microbiology and mathematical biology. One manuscript was recently published led by the Hannover group on the ability of different Campylobacter isolates (from humans and chickens) to colonise chickens and that these induced different immune responses in the chickens PMID 26827832.
Start Year 2011
 
Description DIFAGH 
Organisation University of Bern
Country Switzerland 
Sector Academic/University 
PI Contribution This project represents an EMIDA-ERANET programme linking a number of laboratories together. I lead the overall programme and all research teams including my own are working on a range of collaborative projects. We bring expertise in gut immunology, avian immunology, T/B cell repertoire analyses, innate immunity and infection biology to the consortium.
Collaborator Contribution All of the partners engage in cross-laboratory collaborations. The tasks are divided as follows: Immunity (Oxford and Munich), Germ-free chickens (Munich, Oxford and INRA), Campylobacter infections (Hannover), Salmonella infections (INRA), enterocyte biology (Jerusalem), microbiota biology (Lohmann), microbiome profiling and proteomics (Brno).
Impact A series of publications are currently being prepared, most of which involve multiple partners and can be considered multidisciplinary by brining together expertise across a range of areas including immunology, poultry health, infectious disease, microbiology and mathematical biology. One manuscript was recently published led by the Hannover group on the ability of different Campylobacter isolates (from humans and chickens) to colonise chickens and that these induced different immune responses in the chickens PMID 26827832.
Start Year 2011
 
Description DIFAGH 
Organisation University of Liege
Department Faculty of Veterinary Medicine
Country Belgium 
Sector Academic/University 
PI Contribution This project represents an EMIDA-ERANET programme linking a number of laboratories together. I lead the overall programme and all research teams including my own are working on a range of collaborative projects. We bring expertise in gut immunology, avian immunology, T/B cell repertoire analyses, innate immunity and infection biology to the consortium.
Collaborator Contribution All of the partners engage in cross-laboratory collaborations. The tasks are divided as follows: Immunity (Oxford and Munich), Germ-free chickens (Munich, Oxford and INRA), Campylobacter infections (Hannover), Salmonella infections (INRA), enterocyte biology (Jerusalem), microbiota biology (Lohmann), microbiome profiling and proteomics (Brno).
Impact A series of publications are currently being prepared, most of which involve multiple partners and can be considered multidisciplinary by brining together expertise across a range of areas including immunology, poultry health, infectious disease, microbiology and mathematical biology. One manuscript was recently published led by the Hannover group on the ability of different Campylobacter isolates (from humans and chickens) to colonise chickens and that these induced different immune responses in the chickens PMID 26827832.
Start Year 2011
 
Description Organisation of AIRG 2018 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Organisation of the Avian Immunology Research Group. The largest avian immunology conference in the international calendar. Attracts researchers, industry specialists, students, veterinarians and poultry specialists. We also secured a fund from the Oxford HEFCE GCRF fund to bring 20+ leading poultry researchers from LMIC to the meeting and associated workshop.
Year(s) Of Engagement Activity 2018
 
Description Poultry Health outreach and teaching 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Teaching on the Poultry Health Course aimed at veterinary practitioners, industry and postgraduates. Speaking at industry led events.
Year(s) Of Engagement Activity Pre-2006,2006,2007,2008,