Canada_IPAP Constructing model microbiomes to study microbial interactions and AMR in dairy production systems

Lead Research Organisation: University of Surrey


The World Health Organization considers antimicrobial resistance (AMR) as an urgent global threat to health, livelihood, economies, and environment and a threat to the progress of Sustainable Development Goals. In 2019, 1.27 million deaths were attributed to AMR and this number is predicted to rise to 10 million by 2050 without effective intervention. Antibiotics are routinely used in veterinary medicine for therapeutic and prophylactic purposes, and during routine animal husbandry in many countries. Antibiotics and their metabolites persist in the gastrointestinal tract of animals, and their accumulation at sub-lethal concentrations in the gut induces a selective pressure on the microbiota that facilitates the maintenance of antibiotic-resistant bacteria (ARB) and enrichment of antibiotic resistance genes (ARGs). Food-producing farm animals are prone to pathogen infections and antibiotic treatment, and potentially transmit AMR pathogens to each other, the associated environment, and humans, raising risks to public health.

Consequently, a substantial fraction of antibiotic residues (up to 90%) and their associated ARGs are shed in manure. Animal manure is often spread on land as fertiliser without proper treatment, posing risks of disseminating ARBs and ARGs - with/between indigenous soil populations through horizontal gene transfer (HGT). In the UK, the annual amount of manure used in agriculture is pegged at over 70 million tonnes. Many studies have demonstrated ARB and ARG increases in soil microbiome induced by manure fertilising, which becomes a hotspot for HGT.

From the environment, ARGs may be cycled back to animals through fodder ingestion, direct contact, airborne particles, and runoff to water, the latter three routes also become threats to humans, in addition to the food chain transmission. Effective mitigation strategies are required to reduce AMR levels in the One Health cycle.

This project will combine the expertise from UK and Canada to investigate, in complex microbiomes in dairy cattle and associated environments, how AMR can be affected/controlled by microbial ecological interactions. Field samples from organic and conventional dairy farms in UK and Canada will be analysed and compared on microbiome and AMR. Collective results using shotgun metagenomics tools and high-throughput multiplexed amplicon sequencing and ddPCR methods will generate an overview and detailed information on AMR burden in dairy farms. The project aims to construct isolation libraries and synthetic microbial communities (which improves reproducibility and replications) to create model microbiomes for mechanistic investigations of ecological interactions and AMR. This project will contribute to the long-term goal of AMR transmission mitigation.

Technical Summary

Antimicrobial resistance (AMR) is a global threat to public health and animal health and disseminates through the interconnected human, animal, and environmental reservoirs. The farm animal gastrointestinal tracts and associated environments host diverse microbial communities with complex interspecies interactions. In this context, AMR evolution and transmission need to consider the effect of the ecological processes. Within each environment, interactions such as cross-feeding, competition, signalling communication, and mixed-species biofilm protection may affect the resistance behaviour of AMR pathogens.

This project aims to understand the effect of ecological interactions on AMR and transmission in dairy production systems using synthetic microbial communities. Organic and conventional dairy farms will be compared to evaluate the effect of antibiotic use/absence on AMR. Dairy cattle faecal samples and the associated soil samples will be collected for metagenomics analysis to reveal microbial community composition, functions, antimicrobial resistance genes, and keystone species. A low-cost, low-detection-limit High-throughput Multiplexed Amplicon Sequencing and ddPCR (HMAS-ddPCR) method will be used to analyse allelic diversity by the Canadian partner team.

Both top-down and bottom-up approaches will be used to construct synthetic microbiome. Microbial strains will be isolated from faecal and soil microbiome using a high-throughput Culturomic platform and isolation chips. These isolations will be used to construct synthetic microbial communities AMR using bottom-up approaches.

This project will lay the foundations for long-term research on microbial ecology and AMR, and foster collaborations between UK-Canada researchers. By understanding how ecological interactions affect AMR, we anticipate employing these interactions to mitigate AMR (e.g. new probiotic treatment) and prevent their transmissions across different environments.


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