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Harnessing the gut microbiome to strengthen livestock resilience against carriage and infection by pathogens

Harnessing the gut microbiome to strengthen livestock resilience against carriage and infection by pathogens

  • Animal Disease
  • 2022-2027
Sustainable Development icon: good health and wellbeing
Sustainable Development icon: responsible consumption and production
Sustainable Development icon: life on land

Challenges

Infectious diseases continue to be a significant problem in farmed animals. Diseases such as enteritis, mastitis and uterine infections cause livestock suffering and financial losses for farmers. These issues are made more challenging by the rising prevalence of pathogens with antimicrobial resistance and the need to reduce antibiotic usage on farms. We need novel treatment options, therefore, to reduce the growth and prevalence of pathogens such as toxigenic Escherichia coli to reduce the burden of infectious disease in livestock.

One highly promising avenue is to harness the indigenous microbes (microbiome) of livestock to enhance their defence against invading pathogens. The microbiome protects the host animal via a range of activities, including stimulating the immune system and producing antimicrobial compounds that kill or impede disease-causing microbes. The susceptibility of animals to infectious diseases can therefore be heavily influenced by the composition of their gut microbiome. However, the microbiomes of livestock are complex, and many of the constituent species have either yet to be cultured or are vastly understudied. As a result, it is largely unknown what components of livestock microbiomes are likely to be the most active against pathogens, and that can be developed as novel therapeutic options. In this project, we are therefore aiming to identify livestock microbes, or their products, with inhibitory activity against a range of important pathogens.

Questions

  • For key diseases for livestock in Scotland, which pathogen component and host immune responses will prove useful to exploit as targets for potential vaccines or for accurate detection and diagnoses of infection?
  • What approaches and strategies can combat zoonoses and emerging diseases to protect public health, animal health and antimicrobial resistance in Scotland?

Solutions

Infectious diseases, particularly when caused by antibiotic-resistant pathogens, are major problems in farmed animals. New treatment strategies are needed to reduce infections, and the use of antibiotics in farming environments. We aim to address this by harnessing animal intestinal and environmental microbiomes to boost defence. We will screen our diverse bacterial culture collections to identify health-associated microbes with potent activity against selected pathogens that cause significant economic and health impacts, including antibiotic-resistant strains. The approaches developed in this project also allow us to be responsive to new and emerging pathogens.

This project is:

  • Identifying specific commensal microbes, and associated potential bioactives, from livestock microbiomes that suppress the growth of economically important animal pathogens, such as those that cause gastroenteritis and mastitis.
  • Exploring mechanisms of action by these inhibitory gut commensal microbes and determine their potential for development as novel therapeutics by studying their genomes for beneficial and deleterious traits.
  • Evaluating the ability of identified inhibitory gut microbes to reduce the carriage of pathogens in in-vitro models of the animal gut.

Thus, over the five-year span of this project, we are investigating microbiome links to resilience against infection by important livestock pathogens derived from distinct branches of life (including bacteria and fungi). By identifying candidate microbiome species with the greatest potential as alternative therapeutic targets, the novel information generated should inform attempts to develop new approaches to reduce and minimise the incidence of important disease-causing pathogens in animals.

Project Partners

The Rowett Institute

Progress

2022 / 2023
2022 / 2023

In Year 1 we successfully identified livestock gut-derived microbiome species with antimicrobial activity against the fungal pathogen Candida albicans. We also successfully developed overlay and supernatant assays to assess the ability of cattle and chicken microbiome species to inhibit the growth of bacterial pathogens linked to diarrhoeal disease and skin infections in livestock. From this initial work, we identified a number of promising livestock microbiome species with inhibitory activities against the pathogens Escherichia coli, Klebsiella oxytoca, Clostridium perfringens, Streptococcus uberis and Staphylococcus aureus. These highly encouraging results gave us promising candidates to take forward into subsequent years of the project. 

 

Key Outputs

 

Human microbiome myths and misconceptions (2023) paper published in Nature Microbiology by Alan Walker et al

Questioning the fetal microbiome illustrates pitfalls of low-biomass microbial studies (2023) paper published in Nature by Katherine Kennedy et al

Human gut bifidobacteria inhibit the growth of the opportunistic fungal pathogen Candida albicans (2022) paper published in FEMS Microbiology Ecology by Liviana Ricci et al

Links between intestinal anaerobes, diet and human health (2023) paper published in Biomedicines by Sylvia Duncan et al.

Presentations, reports, non-Gateway blogs etc.,

 

 

  • A blog was written by one of our previous PhD students, Liviana Ricci, for the FEMS Microbiology website, describing some of the work we have done to characterise the anti-fungal activities of gut bifidobacteria - https://fems-microbiology.org/femsmicroblog-fecal-bifidobacteria-inhibit-candida-albicans/
  • We co-organised and hosted an International Gut Microbiology conference (13-15th June, 2023), featuring a dedicated session on the use of the microbiome to reduce infectious disease in animals. This conference attracted around 200 delegates from around the world.
  • Alan Walker had extensive press interviews (e.g. De Standaard, ZME Science, New Scientist, The Hindu, Neue Zurcher Zeitung) in the 2nd half of 2023 to advertise his article published in Nature Microbiology, illustrating myths and misconceptions about the microbiome.
  • Alan Walker attended a Microbiome Policy Meeting at the House of Lords (Millbank House), London, in November 2023. This meeting discussed how we can increase the profile of UK-based microbiome research in a One Health context.
  • Alan walker attended, spoke at, and chaired a session at, a Microbiome Safety Workshop in London in January 2024. This event brought together experts from academia, industry and beyond to discuss the current research landscape around the assessment of the safety of microbiome perturbations by chemicals and probiotics.

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