Monitoring the gut microbiome via AI and omics: a new approach to detect infection and AMR and to support novel therapeutics in broiler precision farm

Lead Research Organisation: University of Nottingham
Department Name: School of Veterinary Medicine and Sci

Abstract

The production of poultry for meat consumption (broilers) is rising globally, the UK being amongst the countries with the highest production. Poultry meat consumption pro capita in the UK is twice more than pork and almost three times more than beef, and growing. Poultry endemic diseases due to bacteria, viruses and parasites are frowned upon, as they can cause considerable economic losses. To save production, the use of broad-spectrum antibiotics at any sign of incipient disease is widespread, even when the source of the disease has not been pinpointed yet (let alone the bacterial origin). The act of administering antibiotics increases the risk of the pathogen developing resistance (antimicrobial resistance - AMR), making it more difficult to fight that pathogen in the future. To reduce the use of broad-spectrum antibiotics, solutions are urgently needed for farms to efficiently monitor livestock, identify infections and the source of infection as soon as possible, and administer more targeted therapeutics.

The project aims at developing new surveillance solutions specifically designed for use by the broiler industry. These solutions are designed to be turn-key: operators will periodically upload data acquired within the farm to a cloud-based service where the state of production will be assessed automatically. Warnings and advice will be sent back to the farmers via apps on smartphones/tablets, in case infections, co-infection or increased likelihood of AMR are detected.
The project will cover the main pathogens of bacterial, viral and parasitic origin affecting UK broiler farming, as well as AMR to the main classes of antibiotics routinely administered in the country.

How will surveillance solutions achieve their predictions, and how will we decide what data to upload? At the core of the project there is a data mining method powered by machine learning, recently perfected by the applicants. The method allows to consider a large amount of heterogeneous information collected from the farm, including historical data of previous infections/AMR events, and allows the development of mathematical models that, based on observing specific patterns in the collected information, estimate the likelihood of infection or resistance manifestations. The method also allows to isolate what farm variables are the most important for each type of prediction (e.g. a specific infection, or AMR trait): these variables are called "biomarkers". Initially, we will consider many variables: sensor data on temperature, humidity, illumination and air composition in the barn, microbiological analysis of samples from feathers, soil, barn floors, water, feed, and operator boots. An important role is reserved to data originating from the analysis of the gut microbiome, i.e. the microbial species living in the broiler gut, whose abundances, genetic traits and metabolic functions, have been proven implicated in numerous aspects of infection and resistance. Co-presence of viruses and parasites will be considered. Thanks to machine learning, for the first time it will be possible to prune such a multitude of variables, isolating the most relevant (biomarkers) to be used in the final prediction models. These models will be turned into software applications running remotely as cloud services. Users (farmers) will periodically upload information (biomarker values) as required, allowing for the models to replicate exactly at any time the state of the real production (models will become "digital twins", being virtual replicas of the real system). Farmers will then receive messages via web-based apps, reporting warnings, alarms, or suggested therapies.
The methods for identifying the important variables and developing prediction models have been successful in pilot studies, leading to the identification of promising biomarkers documented in publications. The projected impact of the project on surveillance in broiler farming is expected to be unprecedented.

Technical Summary

Research on precision livestock farming has been increasingly recognising the importance of studying the gut microbiome, resistome and its metabolites, as an invaluable source of information in relation to animal health and welfare. The population of gut microbiota changes in complex ways, as a consequence of external factors (environment, feed, etc.), but also as a consequence of infection, co-infection, diseases, and therapeutics.

In recent work on diseases and antimicrobial resistance (AMR) in broiler farming, we demonstrated that valuable information can be extracted from the bird gut microbiome. Through the development of a custom data mining method based on machine learning (ML), we uncovered evidence of correlations between gut metagenome modifications (metagenome and composition of the microbial community), environmental variables (temperature and humidity) and the likelihood of finding antimicrobial resistance (AMR) in reference pathogens within the farm (E. coli). We discovered evidence of resistance traits shared by birds, environments, and produced meat, and isolated hot-spots where infections and resistances tend to concentrate the most within the farm.

In this project, we plan to improve our ML methods to include a much larger set of variables. Within the gut, the metabolome and the possible co-presence of viruses and parasites. Within the farm, illumination and air composition, and data from optical/IR imaging and acoustic sensing. Genomics and metagenomics on many additional types of biological samples (barn floors, operator boots, drinking water, dust, air, water reservoir) will be included.
Another novelty aspect will be the development of cloud-based surveillance systems. Technical innovations will be the adoption of cloud services to relieve farms from the burdens of computing and data storage, and the use of digital twins (from Industry 4.0) to support remote surveillance AI, with simple messaging sent back to the farmers.

Publications

10 25 50
 
Description Invited by the World Health Organisation (WHO) as expert, to advise on future potential and application of digital health for AMR prevention and control, for the AMR roadmap 2023-2030 that was adopted by Member States at the Regional Committee 73
Geographic Reach Multiple continents/international 
Policy Influence Type Implementation circular/rapid advice/letter to e.g. Ministry of Health
 
Description Member of official UK delegation to China
Geographic Reach Asia 
Policy Influence Type Contribution to new or improved professional practice
 
Title AI-powered surveillance, diagnostics and treatment selection solutions 
Description AI-powered to: study gut microbiome and metabolome modifications tied to events of infection, co-infection and appearance of resistant traits; study further correlations between gut modifications and external, observable variables; contribute to understanding the dynamics of infection and transmission; identify subsets of observable gut and/or external variables, eligible to act as biomarkers of infection or resistance; turn the mathematical models into digital twins; develop turn-key surveillance, diagnostics and treatment selection solutions 
Type Of Material Technology assay or reagent 
Year Produced 2023 
Provided To Others? No  
Impact Impacts are not available yet 
 
Title Development of an innovative method and software powered by machine learning for better solutions for surveillance, diagnostics and treatment selection applied to livestock farming 
Description We are developing a real-time predictive method that is able to predict know and unknown genes and/or mutations underlying antimicrobial resistance circulating in the farm. The development of the method started earlier however it is from this award that we are developing the capability to correlate microbiome to co-infections and AMR and not just to single infections and AMR. The method relies on machine learning large-scale data mining to unravel the network of possible interactions amongst observable variables I the farm (e.g usage of antibiotics, temperature and humidity), following broilers along their life cycle, and capturing episodes of infection, treatment and development of single or multi-drug resistance. The future application of the method via a cloud system can provide hints at the selection of observable variables acting as biomarkers, i.e, targetable by future solutions for real-time livestock monitoring, to detect/forecast infection or the presence/insurgence of resistant traits, and to support precision diagnostics and bespoke treatment selection. The results may also suggest routes to improve the birds gut microbiome, for example via feed additives, making it more robust to infection while at the same time inhibiting the development of resistance. Our solution may have important implications to fight AMR. The method starts from from whole genome sequence of a specific pathogen or multiple. 2) Use bioinformatics to retrieve from the genome all the core genes, regulatory regions, mutations (single nucleotide polymorphisms - SNPs), mobile genetic elements and also accessory genes which may have been acquired from other pathogens (via horizontal gene transfer). This step results in a large number of interesting candidates (genetic elements) for further investigation. This set may or may not contain previously annotated genes. We select a specific phenotype, that is the resistance/susceptibility profiles to a specific or multiple antibiotic treatments. 4) we use machine learning (ML) to build and train a predictor of the phenotype (e.g. resistance/susceptibility), using as input all the genetic elements found at step 2. Once the trained ML predictor has learned to predict the phenotype well, then it is capable of telling us which genetic elements (regulatory regions, mutations, accessory genes, etc.), alone or in combination, had the bigger influence in determining the correct result, hence exhibiting the highest correlation to the phenotype. The final set of ranked genetic elements returned by ML is typically a reasonably-sized set, which may contain previously annotated genes, but will also contain entirely new ones, mutations, etc. which would have been ignored in more conventional methods. In addition we can: 5) we can repeat the entire procedure, starting from the same pathogen, but considering a new biological sample collected at a different time point, or collected in different conditions (e.g. healthy vs infected, treated vs untreated, etc.) and see whether the method results in different sets of identified genetic elements. This allows us to study temporal modifications as well as condition-driven modifications. 6) to further extend the investigation, we can also perform metagenomics on the same sample used to run our analysis on a given pathogen, thus retrieving types and abundances of the entire microbial population (in this case, the gut microbiome). This paves the way to other types of correlative analyses with the results of pipeline 1-5: what was the microbiome like, when resistance was found in a specific pathogen? How the types and abundances of the entire microbial population changed between time points, treatments, environments? And how these changes affected the resistance/susceptible profiles? 7) The last step is to add any other information acquired contextually to each biological sample. E.g., information from other microbiomes in the surroundings (e.g. soil, water, etc.), environmental sensor data, bird behaviour data, farm management data, etc. As the correlative infrastructure is already established, we can include all the other information incrementally, and again use ML to search for correlations which go beyond the genome-phenotype system, thus achieving an unprecedented depth and breadth of observation. 
Type Of Material Computer model/algorithm 
Year Produced 2023 
Provided To Others? No  
Impact Reduce usage of antibiotics Perform in real-time prediction of known and novel AMR bacterial variants Detect/forecast infection or the presence/insurgence of resistant traits, and to support precision diagnostics and bespoke treatment selection. Provide simple guidelines to farmers on the most adequate antimicrobial treatment 
 
Description INCA: Integrative Network for Combatting Antibiotic Resistance in Humans and Animals 
Organisation British Poultry Council
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution In light of the innovative methods and research cultivated through this BBSRC award and the previous BBSRC award "Fighting Infection and AMR in broiler farming: AI, omics and smart sensing for diagnostics, treatment selection and gut microbiome improvement", Daniel Parker from Slate Hall Veterinary Service, a partner in this BBSRC and previous awards, and I have received an invitation to join the "INCA: Integrative Network for Combatting Antibiotic Resistance in Humans and Animals " consortium, for the application call to the BBSRC-UKRI-Transdisciplinary networks to tackle antimicrobial resistance (AMR), together with Queen's Mary Univeristy, University of Cambridge, Imperial College London and others. The primary objective of this consortium is to pioneer novel approaches for combating AMR through interdisciplinary approaches. My contribution is to provide methods, knowhow on AI, machine learning, One Health.
Collaborator Contribution Daniel Parker has actively contributed to the network's formation, particularly through his engagement with the British Poultry Network within the consortium. As of now, our joint application is currently in the review process.
Impact As of now, our joint application is currently in the review process under BBSRC.
Start Year 2023
 
Description Multi-sector Endemic livestock disease consortium and partnership. 
Organisation AB Agri Ltd
Country United Kingdom 
Sector Private 
PI Contribution Thanks to this award, I was able to form a partnership featuring a unique combination of skills and expertise. The multi-lateral partnership that are directly linked to the award include the one established among: Univ. of Nottingham (UoN, PI: Dottorini); Univ. of Cardiff (UoC); Innovation for Agriculture (IfA); AB Agri Ltd; Agri-food and Biosciences Institute (AFBI), veterinary practitioner (Parker), a poultry integrator and two farms selected by AB Agri. For this specific award and partnership I have set up the consortium, assembled the partners and developed the ideas behind the project design and execution and wrote the entire proposal. For the award I have brought my research experience, management and leadership. I have significant, previous research experience in precision poultry and dairy farming, having developed machine learning solutions for monitoring and diagnostics of infection and antimicrobial resistance. This project capitalises upon work conducted by me and my team in developing computational pipelines that use machine learning (ML) technology to mine correlations between next generation sequencing data, environmental sensing and microbiological analysis, to investigate infection, antimicrobial resistance and transmission between animals, food and the environment. In contexts other than farming, relevant recent results include the identification of novel SCCmec type and variants of methicillin-resistant Staphylococcus aureus (MRSA) shared between food and humans in China (Wang W et al., 2022,J. Antimicrob. Chemother), uncovering a large number of new ARGs which would not have been visible with conventional methods, and the discovery of many new shared ARGs in animal and human isolates from multiple countries, targeting resistance profiles of E. coli to a panel of 12 antibiotics (Pearcy et al., 2022, mSystems ). Of specific interest for this partnership and award are our recent results for livestock farming. In a preliminary study covering one broiler farm in China, we uncovered new ARGs and hot-spots of infections shared by birds and farm environments, using ML methods to mine WGS data from highly resistant pathogenic and non-pathogenic E. coli in broiler guts and farm sources (Peng, et al 2022, Plos Comp Biol). A further expansion of the ML-powered method to data collected from 11 farms across 3 Chinese provinces, targeting hundreds of highly-drug resistant E. coli and S. enteriditis confirmed the robustness of the methods and their capacity in detecting shared ARGs between bacteria co-infecting the same animals (preliminary unpublished data). In Maciel-Guerra, et al. (Maciel-Guerra et al, 2023, ISME J) we proposed an evolution of the ML method to allow the analysis of the gut microbiome, specifically the resistome. The method included also the possibility to search for correlations with environmental sensing data. By analysing one Chinese broiler farm, we identified several clinically relevant shared ARGs and associated mobile genetic elements (bird, farm soil, abattoir surfaces and meat). Importantly, we demonstrated the existence of a core chicken gut resistome that correlates with AMR profiles of E. coli isolates (an important indicator species of AMR in the farm) taken from the same gut samples. The core resistome is itself correlated with temperature and humidity opening novel pathways for surveillance. We have recently further evolved the ML method to incorporate relative abundances of the microbial population in addition to the gut resistome. Large-scale application of the new method to 11 farms in 3 Chinese provinces (460 metagenomic samples collected in 3 years) has led to results confirming previously identified correlations and to unravelling new ones (https://assets.researchsquare.com/files/rs-2458989/v1/46849cd8-3388-46ea-8978-4627d10e99fa.pdf?c=1673626633, under review). All these works have been used to build this award and partnerships. In addition thanks to this award I was bale to set up an additional multi-lateral partnership including a larger consortium. The team expands on the existing core generated by this award with the aim to tackle endemic livestock diseases at a larger scale and include: Hook2sisters (H2S), AB Agri (ABA), Slate Hall Veterinary Services (SH), Greengage (GG), Oxford Nanopore Technology (ONT). In addition the PI of this award Dottorini also included additional colleagues from the University of Nottingham: M.Loose (ML), DH.Kim (DHK)and M.Baker (MB) is a UoN research fellow with expertise in bioinformatics working on poultry infectious diseases.
Collaborator Contribution Regarding the multi-lateral partnership that are directly linked to the award it includes the: Univ. of Nottingham (UoN, PI: Dottorini); Univ. of Cardiff (UoC); Innovation for Agriculture (IfA); AB Agri Ltd; Agri-food and Biosciences Institute (AFBI, Adenuga Adewale), veterinary practitioner (Daniel Parker), a poultry integrator and two farms selected by AB Agri Ltd, Sophie Prentice). AB Agri Ltd is leader in the agri food industry and provides access to the farm and to sensor data; the University of Cardiff (UoC, Nieek Buurma) is active in the Feasibility study on the future realisation of biosensors based on identified biomarkers obtained via machine learning; AFBI provides an assessment of cost-effectiveness, in particular will provide technical and economical feasibility studies to embed biomarkers in solutions for monitoring; Slate Hall Service(Daniel Parker) has expertise in veterinary medicine and co-designed the collection protocols and help in the analysis of the results; IfA: a consortium of English agricultural societies that provides experience and infrastructure for dissemination to farmers and farmers. In addition a larger multi-lateral partnership has resulted from this award. The team expands on the existing core generated by this award with the aim to tackle endemic livestock diseases at a larger scale and include: Hook2sisters (H2S), one the of the five largest poultry producers, growing 6 million chickens a week from their regional sites in Oxfordshire, Yorkshire, Lincolnshire, East Anglia, Devon, Scotland and Wales, will provide farms and oversee their operation during the data collection periods; AB Agri (ABA), the largest UK animal feed, nutrition and agri-food technology producer, will provide consultancy and additional farms if needed (risk mitigation). Slate Hall Veterinary Services (SH), specialist in health and welfare for poultry, will oversee sample collection and monitor poultry health and therapeutics. Greengage (GG), leading provider of sensors for monitoring poultry environment (temperature, humidity, light, CO2, CO, NH3, etc.) and behaviour (vocalization, clustering, mobility), will install and run all the on-farm sensors; Oxford Nanopore Technology (ONT), developer of a new generation of DNA portable sensing technology, will oversee on-field DNA sequencing. In addition to the PI of the award Dottorini also included additional colleagues from the University of Nottingham: M.Loose (ML) is the Director of DeepSeq, the next-generation sequencing facility at UoN, with DH.Kim (DHK) is the Director of the UoN Centre for Analytical Bioscience, and M.Baker (MB) is a UoN research fellow with expertise in bioinformatics working on poultry infectious diseases.
Impact This is a multidisciplinary collaborations embracing bioinformatics, machine learning, veterinary medicine, biosensor technology , microbiology, farm practice and management, smart sensing Outcome: Workshops across all partners including farmers to address challenges and design the next cutting-edge research to tackle livestock endemic diseases Generation of a large multi-disciplinary consortium to address further research questions Application for further funding
Start Year 2022
 
Description Multi-sector Endemic livestock disease consortium and partnership. 
Organisation Agri-Food and Biosciences Institute
Country United Kingdom 
Sector Public 
PI Contribution Thanks to this award, I was able to form a partnership featuring a unique combination of skills and expertise. The multi-lateral partnership that are directly linked to the award include the one established among: Univ. of Nottingham (UoN, PI: Dottorini); Univ. of Cardiff (UoC); Innovation for Agriculture (IfA); AB Agri Ltd; Agri-food and Biosciences Institute (AFBI), veterinary practitioner (Parker), a poultry integrator and two farms selected by AB Agri. For this specific award and partnership I have set up the consortium, assembled the partners and developed the ideas behind the project design and execution and wrote the entire proposal. For the award I have brought my research experience, management and leadership. I have significant, previous research experience in precision poultry and dairy farming, having developed machine learning solutions for monitoring and diagnostics of infection and antimicrobial resistance. This project capitalises upon work conducted by me and my team in developing computational pipelines that use machine learning (ML) technology to mine correlations between next generation sequencing data, environmental sensing and microbiological analysis, to investigate infection, antimicrobial resistance and transmission between animals, food and the environment. In contexts other than farming, relevant recent results include the identification of novel SCCmec type and variants of methicillin-resistant Staphylococcus aureus (MRSA) shared between food and humans in China (Wang W et al., 2022,J. Antimicrob. Chemother), uncovering a large number of new ARGs which would not have been visible with conventional methods, and the discovery of many new shared ARGs in animal and human isolates from multiple countries, targeting resistance profiles of E. coli to a panel of 12 antibiotics (Pearcy et al., 2022, mSystems ). Of specific interest for this partnership and award are our recent results for livestock farming. In a preliminary study covering one broiler farm in China, we uncovered new ARGs and hot-spots of infections shared by birds and farm environments, using ML methods to mine WGS data from highly resistant pathogenic and non-pathogenic E. coli in broiler guts and farm sources (Peng, et al 2022, Plos Comp Biol). A further expansion of the ML-powered method to data collected from 11 farms across 3 Chinese provinces, targeting hundreds of highly-drug resistant E. coli and S. enteriditis confirmed the robustness of the methods and their capacity in detecting shared ARGs between bacteria co-infecting the same animals (preliminary unpublished data). In Maciel-Guerra, et al. (Maciel-Guerra et al, 2023, ISME J) we proposed an evolution of the ML method to allow the analysis of the gut microbiome, specifically the resistome. The method included also the possibility to search for correlations with environmental sensing data. By analysing one Chinese broiler farm, we identified several clinically relevant shared ARGs and associated mobile genetic elements (bird, farm soil, abattoir surfaces and meat). Importantly, we demonstrated the existence of a core chicken gut resistome that correlates with AMR profiles of E. coli isolates (an important indicator species of AMR in the farm) taken from the same gut samples. The core resistome is itself correlated with temperature and humidity opening novel pathways for surveillance. We have recently further evolved the ML method to incorporate relative abundances of the microbial population in addition to the gut resistome. Large-scale application of the new method to 11 farms in 3 Chinese provinces (460 metagenomic samples collected in 3 years) has led to results confirming previously identified correlations and to unravelling new ones (https://assets.researchsquare.com/files/rs-2458989/v1/46849cd8-3388-46ea-8978-4627d10e99fa.pdf?c=1673626633, under review). All these works have been used to build this award and partnerships. In addition thanks to this award I was bale to set up an additional multi-lateral partnership including a larger consortium. The team expands on the existing core generated by this award with the aim to tackle endemic livestock diseases at a larger scale and include: Hook2sisters (H2S), AB Agri (ABA), Slate Hall Veterinary Services (SH), Greengage (GG), Oxford Nanopore Technology (ONT). In addition the PI of this award Dottorini also included additional colleagues from the University of Nottingham: M.Loose (ML), DH.Kim (DHK)and M.Baker (MB) is a UoN research fellow with expertise in bioinformatics working on poultry infectious diseases.
Collaborator Contribution Regarding the multi-lateral partnership that are directly linked to the award it includes the: Univ. of Nottingham (UoN, PI: Dottorini); Univ. of Cardiff (UoC); Innovation for Agriculture (IfA); AB Agri Ltd; Agri-food and Biosciences Institute (AFBI, Adenuga Adewale), veterinary practitioner (Daniel Parker), a poultry integrator and two farms selected by AB Agri Ltd, Sophie Prentice). AB Agri Ltd is leader in the agri food industry and provides access to the farm and to sensor data; the University of Cardiff (UoC, Nieek Buurma) is active in the Feasibility study on the future realisation of biosensors based on identified biomarkers obtained via machine learning; AFBI provides an assessment of cost-effectiveness, in particular will provide technical and economical feasibility studies to embed biomarkers in solutions for monitoring; Slate Hall Service(Daniel Parker) has expertise in veterinary medicine and co-designed the collection protocols and help in the analysis of the results; IfA: a consortium of English agricultural societies that provides experience and infrastructure for dissemination to farmers and farmers. In addition a larger multi-lateral partnership has resulted from this award. The team expands on the existing core generated by this award with the aim to tackle endemic livestock diseases at a larger scale and include: Hook2sisters (H2S), one the of the five largest poultry producers, growing 6 million chickens a week from their regional sites in Oxfordshire, Yorkshire, Lincolnshire, East Anglia, Devon, Scotland and Wales, will provide farms and oversee their operation during the data collection periods; AB Agri (ABA), the largest UK animal feed, nutrition and agri-food technology producer, will provide consultancy and additional farms if needed (risk mitigation). Slate Hall Veterinary Services (SH), specialist in health and welfare for poultry, will oversee sample collection and monitor poultry health and therapeutics. Greengage (GG), leading provider of sensors for monitoring poultry environment (temperature, humidity, light, CO2, CO, NH3, etc.) and behaviour (vocalization, clustering, mobility), will install and run all the on-farm sensors; Oxford Nanopore Technology (ONT), developer of a new generation of DNA portable sensing technology, will oversee on-field DNA sequencing. In addition to the PI of the award Dottorini also included additional colleagues from the University of Nottingham: M.Loose (ML) is the Director of DeepSeq, the next-generation sequencing facility at UoN, with DH.Kim (DHK) is the Director of the UoN Centre for Analytical Bioscience, and M.Baker (MB) is a UoN research fellow with expertise in bioinformatics working on poultry infectious diseases.
Impact This is a multidisciplinary collaborations embracing bioinformatics, machine learning, veterinary medicine, biosensor technology , microbiology, farm practice and management, smart sensing Outcome: Workshops across all partners including farmers to address challenges and design the next cutting-edge research to tackle livestock endemic diseases Generation of a large multi-disciplinary consortium to address further research questions Application for further funding
Start Year 2022
 
Description Multi-sector Endemic livestock disease consortium and partnership. 
Organisation Cardiff University
Country United Kingdom 
Sector Academic/University 
PI Contribution Thanks to this award, I was able to form a partnership featuring a unique combination of skills and expertise. The multi-lateral partnership that are directly linked to the award include the one established among: Univ. of Nottingham (UoN, PI: Dottorini); Univ. of Cardiff (UoC); Innovation for Agriculture (IfA); AB Agri Ltd; Agri-food and Biosciences Institute (AFBI), veterinary practitioner (Parker), a poultry integrator and two farms selected by AB Agri. For this specific award and partnership I have set up the consortium, assembled the partners and developed the ideas behind the project design and execution and wrote the entire proposal. For the award I have brought my research experience, management and leadership. I have significant, previous research experience in precision poultry and dairy farming, having developed machine learning solutions for monitoring and diagnostics of infection and antimicrobial resistance. This project capitalises upon work conducted by me and my team in developing computational pipelines that use machine learning (ML) technology to mine correlations between next generation sequencing data, environmental sensing and microbiological analysis, to investigate infection, antimicrobial resistance and transmission between animals, food and the environment. In contexts other than farming, relevant recent results include the identification of novel SCCmec type and variants of methicillin-resistant Staphylococcus aureus (MRSA) shared between food and humans in China (Wang W et al., 2022,J. Antimicrob. Chemother), uncovering a large number of new ARGs which would not have been visible with conventional methods, and the discovery of many new shared ARGs in animal and human isolates from multiple countries, targeting resistance profiles of E. coli to a panel of 12 antibiotics (Pearcy et al., 2022, mSystems ). Of specific interest for this partnership and award are our recent results for livestock farming. In a preliminary study covering one broiler farm in China, we uncovered new ARGs and hot-spots of infections shared by birds and farm environments, using ML methods to mine WGS data from highly resistant pathogenic and non-pathogenic E. coli in broiler guts and farm sources (Peng, et al 2022, Plos Comp Biol). A further expansion of the ML-powered method to data collected from 11 farms across 3 Chinese provinces, targeting hundreds of highly-drug resistant E. coli and S. enteriditis confirmed the robustness of the methods and their capacity in detecting shared ARGs between bacteria co-infecting the same animals (preliminary unpublished data). In Maciel-Guerra, et al. (Maciel-Guerra et al, 2023, ISME J) we proposed an evolution of the ML method to allow the analysis of the gut microbiome, specifically the resistome. The method included also the possibility to search for correlations with environmental sensing data. By analysing one Chinese broiler farm, we identified several clinically relevant shared ARGs and associated mobile genetic elements (bird, farm soil, abattoir surfaces and meat). Importantly, we demonstrated the existence of a core chicken gut resistome that correlates with AMR profiles of E. coli isolates (an important indicator species of AMR in the farm) taken from the same gut samples. The core resistome is itself correlated with temperature and humidity opening novel pathways for surveillance. We have recently further evolved the ML method to incorporate relative abundances of the microbial population in addition to the gut resistome. Large-scale application of the new method to 11 farms in 3 Chinese provinces (460 metagenomic samples collected in 3 years) has led to results confirming previously identified correlations and to unravelling new ones (https://assets.researchsquare.com/files/rs-2458989/v1/46849cd8-3388-46ea-8978-4627d10e99fa.pdf?c=1673626633, under review). All these works have been used to build this award and partnerships. In addition thanks to this award I was bale to set up an additional multi-lateral partnership including a larger consortium. The team expands on the existing core generated by this award with the aim to tackle endemic livestock diseases at a larger scale and include: Hook2sisters (H2S), AB Agri (ABA), Slate Hall Veterinary Services (SH), Greengage (GG), Oxford Nanopore Technology (ONT). In addition the PI of this award Dottorini also included additional colleagues from the University of Nottingham: M.Loose (ML), DH.Kim (DHK)and M.Baker (MB) is a UoN research fellow with expertise in bioinformatics working on poultry infectious diseases.
Collaborator Contribution Regarding the multi-lateral partnership that are directly linked to the award it includes the: Univ. of Nottingham (UoN, PI: Dottorini); Univ. of Cardiff (UoC); Innovation for Agriculture (IfA); AB Agri Ltd; Agri-food and Biosciences Institute (AFBI, Adenuga Adewale), veterinary practitioner (Daniel Parker), a poultry integrator and two farms selected by AB Agri Ltd, Sophie Prentice). AB Agri Ltd is leader in the agri food industry and provides access to the farm and to sensor data; the University of Cardiff (UoC, Nieek Buurma) is active in the Feasibility study on the future realisation of biosensors based on identified biomarkers obtained via machine learning; AFBI provides an assessment of cost-effectiveness, in particular will provide technical and economical feasibility studies to embed biomarkers in solutions for monitoring; Slate Hall Service(Daniel Parker) has expertise in veterinary medicine and co-designed the collection protocols and help in the analysis of the results; IfA: a consortium of English agricultural societies that provides experience and infrastructure for dissemination to farmers and farmers. In addition a larger multi-lateral partnership has resulted from this award. The team expands on the existing core generated by this award with the aim to tackle endemic livestock diseases at a larger scale and include: Hook2sisters (H2S), one the of the five largest poultry producers, growing 6 million chickens a week from their regional sites in Oxfordshire, Yorkshire, Lincolnshire, East Anglia, Devon, Scotland and Wales, will provide farms and oversee their operation during the data collection periods; AB Agri (ABA), the largest UK animal feed, nutrition and agri-food technology producer, will provide consultancy and additional farms if needed (risk mitigation). Slate Hall Veterinary Services (SH), specialist in health and welfare for poultry, will oversee sample collection and monitor poultry health and therapeutics. Greengage (GG), leading provider of sensors for monitoring poultry environment (temperature, humidity, light, CO2, CO, NH3, etc.) and behaviour (vocalization, clustering, mobility), will install and run all the on-farm sensors; Oxford Nanopore Technology (ONT), developer of a new generation of DNA portable sensing technology, will oversee on-field DNA sequencing. In addition to the PI of the award Dottorini also included additional colleagues from the University of Nottingham: M.Loose (ML) is the Director of DeepSeq, the next-generation sequencing facility at UoN, with DH.Kim (DHK) is the Director of the UoN Centre for Analytical Bioscience, and M.Baker (MB) is a UoN research fellow with expertise in bioinformatics working on poultry infectious diseases.
Impact This is a multidisciplinary collaborations embracing bioinformatics, machine learning, veterinary medicine, biosensor technology , microbiology, farm practice and management, smart sensing Outcome: Workshops across all partners including farmers to address challenges and design the next cutting-edge research to tackle livestock endemic diseases Generation of a large multi-disciplinary consortium to address further research questions Application for further funding
Start Year 2022
 
Description Partnership with France, Italy, South Africa and Switzerland research organisations, academics and companies that led to the funded MRC project MR/Y034422/1 
Organisation Agroscope
Country Switzerland 
Sector Public 
PI Contribution The partnership with the University of Pretoria (South Africa), the French Agency for Food, the Environmental and Health Safety (France), Agroscope, Food Microbial Systems (Switzerland), Flox-AI (UK), Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (Italy) and the University of Milan (Italy) led to the JPIAMR award
Collaborator Contribution We have co-developed and co-designed the interdisciplinary project proposal and research activities.
Impact The funded research will start on June 2024
Start Year 2023
 
Description Partnership with France, Italy, South Africa and Switzerland research organisations, academics and companies that led to the funded MRC project MR/Y034422/1 
Organisation Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Country Italy 
Sector Hospitals 
PI Contribution The partnership with the University of Pretoria (South Africa), the French Agency for Food, the Environmental and Health Safety (France), Agroscope, Food Microbial Systems (Switzerland), Flox-AI (UK), Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (Italy) and the University of Milan (Italy) led to the JPIAMR award
Collaborator Contribution We have co-developed and co-designed the interdisciplinary project proposal and research activities.
Impact The funded research will start on June 2024
Start Year 2023
 
Description Partnership with France, Italy, South Africa and Switzerland research organisations, academics and companies that led to the funded MRC project MR/Y034422/1 
Organisation French Agency for Food, Environmental and Occupational Health & Safety (ANSES)
Country France 
Sector Public 
PI Contribution The partnership with the University of Pretoria (South Africa), the French Agency for Food, the Environmental and Health Safety (France), Agroscope, Food Microbial Systems (Switzerland), Flox-AI (UK), Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (Italy) and the University of Milan (Italy) led to the JPIAMR award
Collaborator Contribution We have co-developed and co-designed the interdisciplinary project proposal and research activities.
Impact The funded research will start on June 2024
Start Year 2023
 
Description Partnership with France, Italy, South Africa and Switzerland research organisations, academics and companies that led to the funded MRC project MR/Y034422/1 
Organisation University of Pretoria
Department Department of Veterinary Tropical Diseases
Country South Africa 
Sector Academic/University 
PI Contribution The partnership with the University of Pretoria (South Africa), the French Agency for Food, the Environmental and Health Safety (France), Agroscope, Food Microbial Systems (Switzerland), Flox-AI (UK), Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (Italy) and the University of Milan (Italy) led to the JPIAMR award
Collaborator Contribution We have co-developed and co-designed the interdisciplinary project proposal and research activities.
Impact The funded research will start on June 2024
Start Year 2023
 
Description China International Food Safety & Quality Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Invited Speaker to the "China International Food Safety & Quality Conference" my presentation was in the section "Application of Omics and
AI Technology in Detection and Control of Microbial in Food". My presentation title was "Investigating AMR Through a One Health Approach Combining Multi-sensing, Omics and Big Data Mining with AI - Applications to Surveillance, Early Warning, Diagnostics and Treatment Selection"
Year(s) Of Engagement Activity 2023
URL http://www.chinafoodsafety.com
 
Description Nottingham researchers joins in the UK's fight against endemic livestock disease 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact This was a press release to make the wider audience aware of the initiative, the people involved and potential outcomes. This was done to foster collaboration
Year(s) Of Engagement Activity 2023
URL https://www.nottingham.ac.uk/news/endemic-livestock-disease