Reducing antibiotic dependence in poultry through immune reprogramming

The findings, published in The Journal of Immunology, suggest that sodium butyrate, a short-chain fatty acid produced by gut bacteria, can train chickens' immune systems to respond more aggressively to bacterial infections.

For an industry facing growing pressure to improve bird health while tackling antimicrobial resistance (AMR), the research offers a glimpse of a future where nutrition and gut health management can enhance immune performance rather than routine medication.

Tackling bacterial diseases

Bacterial diseases remain one of the most significant challenges for poultry production worldwide. Pathogens such as Salmonella and avian pathogenic E. coli (APEC) can affect flock performance, welfare and profitability. At the same time, regulators and supply chains continue to encourage more responsible antibiotic use because overuse contributes to the emergence of antimicrobial resistance.

The research team from the University of Bristol investigated how sodium butyrate interacts with developing chicken immune cells known as macrophages. These cells play a vital role in identifying and destroying invading pathogens. Scientists discovered that exposing immature macrophages to sodium butyrate effectively reprogrammed them, giving them a stronger ability to combat a range of harmful bacteria later in life.

Laboratory testing showed that the trained immune cells exhibited enhanced killing activity against several important pathogens, including E. coli, Salmonella, Pseudomonas aeruginosa and Staphylococcus aureus. According to the researchers, this broad-spectrum response suggests that immune reprogramming may provide benefits against multiple bacterial threats rather than targeting a single disease.

Timing is critical

One of the study's most significant findings was the importance of timing. The immune-enhancing effect only occurred when sodium butyrate was introduced during the early developmental stages of the macrophages. Mature immune cells did not respond in the same way. This discovery could have important implications for how future interventions are designed and implemented in commercial poultry systems.

Unlike some immune training approaches that stimulate strong inflammatory responses, sodium butyrate appears to work through a different pathway. Researchers found that it boosts the production of reactive oxygen species while also increasing autophagy, a natural cellular process that helps identify, trap and destroy invading microbes. The result is a more effective antimicrobial response without the high levels of inflammation that can damage tissues and affect performance.

Professor Shahriar Behboudi, professor of immunology at Bristol Veterinary School and lead author, said the findings expand current understanding of trained immunity and demonstrate that natural metabolites can enhance disease resistance through non-inflammatory mechanisms.

“Our findings suggest that trained immunity exists along a much wider spectrum of phenotypes than previously thought,” he said, adding, “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.”

Potential for poultry production

From an industry perspective, the work reinforces growing interest in the relationship between gut health, microbiome management and immune resilience. Sodium butyrate is already familiar to many poultry nutritionists and feed manufacturers because of its positive effects on gut integrity and performance. The possibility that it may also influence long-term immune function could open new opportunities for preventive health strategies.

While further research will be required to translate the laboratory findings into commercial practice, the study provides a strong scientific foundation for exploring how natural metabolic compounds can support healthier flocks. As poultry producers continue seeking sustainable alternatives to antibiotics, immune reprogramming could become an important tool in the next generation of disease management strategies.

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.