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.
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.
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.
Organisations
- University of Nottingham (Lead Research Organisation, Project Partner)
- Dept for Env Food & Rural Affairs DEFRA (Co-funder)
- Department of Agriculture, Environment and Rural Affairs (DAERA) (Co-funder)
- SCOTTISH GOVERNMENT (Co-funder)
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (Collaboration)
- Agroscope (Collaboration)
- French Agency for Food, Environmental and Occupational Health & Safety (ANSES) (Collaboration)
- British Poultry Council (Collaboration)
- University of Pretoria (Collaboration)
- Hook2Sisters Ltd (Project Partner)
- Oxford Nanopore Technologies PLC (Project Partner)
- AB Agri (Project Partner)
- Greengage Lighting (Project Partner)
- Slate Hall Veterinary Services Ltd (Project Partner)
- University of Perugia (Project Partner)
| 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 |
| Description | Policy Brief On antimicrobial resistance: we know enough to act. The Policy brief was coordinated by the UK Academy of Medical Science. My contribution was on global One Health surveillance approach to fight AMR using Artificial Intelligence and big data mining. Addressing antimicrobial resistance with a One Health approach Symposium. The Academy of Medical Science |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Contribution to a national consultation/review |
| Impact | We organised a workshop and engaged in YK-India discussion about AMR and the outcome was to write a Policy brief on antimicrobial resistance: we know enough to act. This was coordinated by the UK Academy of Medical Science Brief. |
| URL | https://acmedsci.ac.uk/file-download/70131697?utm_source=createsend&utm_medium=email&utm_campaign=am... |
| 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 | 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 | Chair and organiser of the "Tackling the Pandemic of Antimicrobial Resistance and Infection: Developing a Novel Approach to Antimicrobial Surveillance and Early Warning in the UK and China - A Collaborative Approach Between the UK and China" funded by the UK FCDO, November 2024 China National Academy of Science, Beijing, China |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | Chair and organiser of the "Tackling the Pandemic of Antimicrobial Resistance and Infection: Developing a Novel Approach to Antimicrobial Surveillance and Early Warning in the UK and China - A Collaborative Approach Between the UK and China" funded by the UK FCDO, November 2024 China National Academy of Science, Beijing, China |
| Year(s) Of Engagement Activity | 2024 |
| 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 | Invited Speaker FightAMR project to develop the first EU-Africa AI powered surveillance solution. AMR INSIGHTS conference, June 2024 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | This is a Talk at an international conference with Universities and businesses to disseminate project results and foster collaboration |
| Year(s) Of Engagement Activity | 2024 |
| URL | https://www.amr-insights.eu/adtca-2024/program/ |
| Description | Invited key note speaker: "Machine learning and bioinformatics to investigate antimicrobial resistance in host-pathogen interactions", East Midlands Microbiome Research Network (EMMRN) Research Day conference 2024 |
| 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 | Invited key note speaker: "Machine learning and bioinformatics to investigate antimicrobial resistance in host-pathogen interactions", East Midlands Microbiome Research Network (EMMRN) Research Day conference 2024. This was a Research Network among Scientists to disseminate research and network |
| Year(s) Of Engagement Activity | 2024 |
| URL | https://www.medilinkmidlands.com/event/in-person-medilink-midlands-summer-networking-2/ |
| Description | Invited speaker: Novel global One Health surveillance approach to fight AMR using Artificial Intelligence and big data mining. Addressing antimicrobial resistance with a One Health approach Symposium. The Academy of Medical Science |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Invited speaker: Novel global One Health surveillance approach to fight AMR using Artificial Intelligence and big data mining. Addressing antimicrobial resistance with a One Health approach Symposium. The Academy of Medical Science. This activity was done to write a report on AMR in the UK and India. |
| Year(s) Of Engagement Activity | 2024 |
| URL | https://acmedsci.ac.uk/file-download/70131697?utm_source=createsend&utm_medium=email&utm_campaign=am... |
| 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 |
