Harnessing the gut microbiome to strengthen livestock resilience against carriage and infection by pathogens
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
Progress
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.
Publications
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.
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Knowledge exchange and other outputs
- 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 continued our screening assays in Year 2, incorporating a wider range of livestock bacteria and tests, to help us identify the microbiome species with the greatest inhibitory activity against pathogens. In total well over 100 microbiome species were tested, and our results demonstrated that a significant proportion of these species were able to inhibit at least one of the pathogens tested. Importantly, we also showed that inhibitory microbiome species were able to inhibit the growth of more than one type of each pathogen, including some strains that are resistant to multiple antibiotics.
We then began experiments that investigate the potential mechanisms of action that underpin antibacterial activities and allow us to assess suitability of some of our most active livestock gut bacteria as candidate novel therapeutic products. This includes generating genome sequences from the inhibitory microbiome and environmental species, which will allow us to mine these genomes for further clues to the mechanisms underpinning inhibition of pathogens. The latter work will continue into Years 3 and 4.
Publications
- Links between Diet, Intestinal Anaerobes, Microbial Metabolites and Health (2023) paper published in Biomedicines by Sylvia Duncan et al.
- Human microbiome myths and misconceptions (2023) article published in Nature Microbiology by Alan Walker and Lesley Hoyle
Knowledge exchange and other outputs
- Alan Walker was a speaker at a RANK Forum workshop in June 2023, discussing the impact of food security inequalities on health, with a focus on impacts mediated by the gut microbiome.
- Alan Walker and Sylvia Duncan were co-organisers of the 13th biennial International Gut Microbiology Symposium (13-15th June 2023) which included a scientific session on “Interactions between microbiota, pathogens and host”.
- Alan Walker carried out extensive press interviews (e.g. De Standaard, ZME Science, New Scientist, The Hindu, Neue Zurcher Zeitung) to advertise one of his articles, published in Nature Microbiology, illustrating myths and misconceptions about the microbiome. Several other news outlets from around the world picked up the news story and ran articles about it (https://nature.altmetric.com/details/152191319/news).
- Sylvia Duncan participated in Rowett Research Day, presenting a talk entitled: “Synergising one health solutions against pathogens and antimicrobial resistance”
- Alan Walker was a participant at a meeting at the House of Lords in November 2023, aimed at improving the visibility of UK microbiome research.
- Alan Walker was a guest on the "Inside Matters" podcast series, talking about gut health and microbiomes.
- Alan Walker was a speaker and session chair at a microbiome safety workshop in London, organised in January 2024 by the Microbiology Society, to assess the potential safety concerns around microbiome-targeted interventions.
- Sylvia Duncan participated in a discussion group meeting with Scottish farmers, food producers and an Aberdeenshire councillor (Industry support executive) on One Health and the environment
- Sylvia Duncan wrote an article for The Conversation on one of our gut microbiota species with inhibitory activity against multiple pathogens – Gut Microbiome: meet Ruminococcus bromii – the microbe that loves carbs.
- Alan Walker received ~£400k research funding from an industrial partner for a two-year research project to cultivate gut bacteria.
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