Gut molecule reprograms chicken immune cells to fight bacteria without antibiotics

University of Bristol–led researchers have identified a naturally occurring gut molecule that can strengthen chickens' immune response against a wide range of bacterial infections. The study, published August 12 in The Journal of Immunology, demonstrates that sodium butyrate, a short-chain fatty acid produced by gut bacteria, acts as an immune system programmer when introduced during early macrophage development.

Working with primary chicken immune cells and cell lines, the team exposed developing macrophages to sodium butyrate and found the reprogrammed cells showed dramatically increased ability to kill multiple strains of dangerous bacteria, including E. coli, Salmonella, Pseudomonas aeruginosa, and Staphylococcus aureus. The immune enhancement only occurred when the molecule was introduced during early, plastic stages of immune cell development; mature cells did not respond to the treatment.

Unlike traditional immune training agents that cause tissue-damaging inflammation, sodium butyrate works through an alternative pathway. It boosts production of reactive oxygen species and accelerates autophagy, a cellular self-cleaning process that traps and digests invading bacteria. This non-inflammatory mechanism avoids the collateral damage associated with excessive immune activation.

Professor Shahriar Behboudi of Bristol Veterinary School, senior author of the study, said the findings suggest trained immunity exists along a wider spectrum of phenotypes than previously thought. Dr. James Adams, first author and research fellow at the University of Surrey, emphasized the urgency of developing new ways to control bacterial infections in poultry as antimicrobial resistance complicates disease management.

The research provides a framework for designing nature-positive farming systems that could reduce reliance on antibiotics. Overuse of antibiotics in agriculture contributes directly to the global antimicrobial resistance crisis, which threatens both animal and human medicine. Poultry is a major global food source, and protecting flocks using natural metabolic compounds could improve animal welfare and food security.

The study was conducted in vitro using chicken macrophage cell lines and primary cells. The researchers note that translating these findings to real-world farming will require determining precise timing for in vivo application, as the reprogramming window is limited to early immune cell development. The team hopes the findings will pave the way for new gut-health strategies in everyday agriculture.