Dietary modulation of endogenous host defense peptide synthesis as an alternative approach to in-feed antibiotics

Traditionally, antibiotics are included in animal feed at subtherapeutic levels for growth promotion and disease prevention. However, recent links between in-feed antibiotics and a rise in antibiotic-resistant pathogens have led to a ban of all antibiotics in livestock production by the European Union in January 2006 and a removal of medically important antibiotics in animal feeds in the United States in January 2017. An urgent need arises for antibiotic alternatives capable of maintaining animal health and productivity without triggering antimicrobial resistance. Host defense peptides (HDP) are a critical component of the animal innate immune system with direct antimicrobial and immunomodulatory activities. While in-feed supplementation of recombinant or synthetic HDP appears to be effective in maintaining animal performance and alleviating clinical symptoms in the context of disease, dietary modulation of the synthesis of endogenous host defense peptides has emerged as a cost-effective, antibiotic-alternative approach to disease control and prevention. Several different classes of small-molecule compounds have been found capable of promoting HDP synthesis. Among the most efficacious compounds are butyrate and vitamin D. Moreover, butyrate and vitamin D synergize with each other in enhancing HDP synthesis. This review will focus on the regulation of HDP synthesis by butyrate and vitamin D in humans, chickens, pigs, and cattle and argue for potential application of HDP-inducing compounds in antibiotic-free livestock production.