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

Abstract

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.

Dietary supplementation of recombinant antimicrobial peptide Epinephelus lanceolatus piscidin improves growth performance and immune response in Gallus gallus domesticus

“…Histological analysis showed that duodenum villus height was significantly greater in rEP animals than that in the control group (S3a- S3d Fig). Moreover, growth enhancement has been observed in other reports [37,38]. For example, feeding mice with PR39 peptide (4.7 kDa proline-rich AMP)-expressing Lactobacillus casei caused jejunum and duodenum villus height in the intestinal villi to increase [39].…”

Nutritional Intervention for the Intestinal Development and Health of Weaned Pigs

“…Antimicrobial peptides, also known as host defense peptides, have been considered as potential alternatives to antibiotics in livestock and poultry (133–135). Antimicrobial peptides are polypeptides, naturally produced by different organisms from prokaryotes to mammals.…”

“…There are two ways to incorporate the benefits of antimicrobial peptides into animal health and nutrition. One is direct supplementation of exogenous antimicrobial peptides to animal feed, while the other one is to use dietary supplements/ingredients to stimulate the secretion of endogenous antimicrobial peptides by the host (135). Although exogenous or recombinant antimicrobial peptides have shown a great potential to be used as alternatives to replace antibiotics, the effectiveness of those candidates should be carefully verified because the majority of exogenous antimicrobial peptides would be digested in the upper gastrointestinal tract without reaching to the lower part where most pathogens reside.…”

“…Therefore, the stimulation of endogenous antimicrobial peptides secretion by nutritional manipulation may be a better approach. For instance, Robinson et al (135) have completely reviewed the regulation of antimicrobial peptides synthesis by butyrate and vitamin D in livestock and poultry and pointed out the importance of antimicrobial peptides-inducing compounds in antibiotic-free animal production.…”

Molecular characterization, mRNA gene expression, and antimicrobial activity of 2 new cathelicidin genes in goose

“…On the account of the cost and stability for the direct administration of HDPs, indirect instigation of synthesis of endogenous HDPs by dietary compounds seems to be a convenient and cost-effective strategy in animal production ( Deng et al., 2018 , Lyu et al., 2018 ). Because these HDP-inducing compounds have no direct interactions with pathogens, they can boost the synthesis of HDPs without triggering resistance and provoking inflammation ( Zhang and Sunkara, 2014 , Robinson et al., 2018 ). The discovery of the 2 cathelicidin genes in the present study will help explore novel antimicrobial strategy in the future.…”