It has long been a challenge in agriculture to protect livestock from widespread pathogens like Salmonella and Avian Pathogenic E. coli (APEC) without relying heavily on antibiotics. Overuse of these drugs in farming contributes directly to the global crisis of antimicrobial resistance (AMR), which threatens both animal and human medicine.
Working with primary chicken immune cells and cell lines, the research team traced how sodium butyrate, a short-chain fatty acid naturally produced by gut bacteria, acts as an immune system programmer. By exposing developing immune cells, called macrophages, to this compound, the researchers successfully trained the chickens' natural immune defences to fight future infections.
The study found that these reprogrammed chicken immune cells showed a dramatic increase in their ability to kill a wide range of dangerous bacteria, including multiple strains of E. coli, Salmonella, Pseudomonas aeruginosa, and Staphylococcus aureus.
Crucially, the research found a time frame within which the immune reprogramming takes place. The immune system upgrade only occurs if the molecule is introduced during the early, plastic stages of the immune cells' development. When applied to fully mature cells, the treatment failed to improve their disease-fighting capabilities, providing vital clues for how this method must be timed in real-world farming.
Unlike traditional immune training agents that cause high levels of tissue-damaging inflammation, sodium butyrate works through an alternative, cleaner route. It encourages cells to use a precise two-pronged internal attack: boosting the production of destructive oxygen molecules (reactive oxygen species) and accelerating 'autophagy', a cellular self-cleaning process that traps and digests invading germs.
Shahriar Behboudi, Professor of Immunology in the Bristol Veterinary School and senior author of the study, said: "Our findings suggest that trained immunity exists along a much wider spectrum of phenotypes than previously thought.
"By demonstrating that a natural gut metabolite can program immune cells through an alternative, non-inflammatory axis, we open up exciting new possibilities for enhancing animal health naturally, without the collateral damage of excessive inflammation."
Dr James Adams, a Research Fellow in the School of Veterinary Medicine at the University of Surrey and the first author on the paper, added: "The increasing spread of diseases amongst chickens is of great concern. Bacterial diseases cause significant animal health and welfare issues in poultry, incurring devastating economic losses and potential disruption to our food chain.
"Antimicrobial resistance is complicating the management of disease in poultry. Therefore, it is crucial that we develop new ways of controlling bacterial infections in poultry."
The study's findings offer a vital framework to help the poultry industry and policymakers design nature-positive farming systems.
As poultry is a major global food source, protecting flocks from disease using natural metabolic compounds is essential for both food security and sustainable development.
The team hopes these findings will pave the way for new gut-health strategies in everyday agriculture, improving animal welfare and reducing the world's reliance on antibiotics.
The collaborative research, led by the University of Bristol, the University of Surrey, and The Pirbright Institute, was funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and the British Egg Marketing Board Research and Education Trust.
Paper
'Innate immune reprogramming of chicken macrophages by sodium butyrate enhances ROS-mediated antimicrobial responses in vitro' by Shahriar Behboudi et al. in The Journal of Immunology [open access]
