Induction of Porcine Host Defense Peptide Gene Expression by Short-Chain Fatty Acids and Their Analogs

Abstract

Dietary modulation of the synthesis of endogenous host defense peptides (HDPs) represents a novel antimicrobial approach for disease control and prevention, particularly against antibiotic-resistant infections. However, HDP regulation by dietary compounds such as butyrate is species-dependent. To examine whether butyrate could induce HDP expression in pigs, we evaluated the expressions of a panel of porcine HDPs in IPEC-J2 intestinal epithelial cells, 3D4/31 macrophages, and primary monocytes in response to sodium butyrate treatment by real-time PCR. We revealed that butyrate is a potent inducer of multiple, but not all, HDP genes. Porcine β-defensin 2 (pBD2), pBD3, epididymis protein 2 splicing variant C (pEP2C), and protegrins were induced markedly in response to butyrate, whereas pBD1 expression remained largely unaltered in any cell type. Additionally, a comparison of the HDP-inducing efficacy among saturated free fatty acids of different aliphatic chain lengths revealed that fatty acids containing 3–8 carbons showed an obvious induction of HDP expression in IPEC-J2 cells, with butyrate being the most potent and long-chain fatty acids having only a marginal effect. We further investigated a panel of butyrate analogs for their efficacy in HDP induction, and found glyceryl tributyrate, benzyl butyrate, and 4-phenylbutyrate to be comparable with butyrate. Identification of butyrate and several analogs with a strong capacity to induce HDP gene expression in pigs provides attractive candidates for further evaluation of their potential as novel alternatives to antibiotics in augmenting innate immunity and disease resistance of pigs.

Alternatives to the use of antimicrobial agents in pig production: A multi-country expert-ranking of perceived effectiveness, feasibility and return on investment

“…Improved feeding strategies and the use of organic acids related to pig health are described by Heo et al (2012) and Visscher et al (2008) amongst others. Dietary modulation by means of peptides through short-chain fatty acids is another promising feed related alternative to antimicrobial agents (Zeng et al, 2013).…”

Butyrate upregulates endogenous host defense peptides to enhance disease resistance in piglets via histone deacetylase inhibition

“…Butyrate, a major species of short-chain fatty acid (SCFA) produced by bacterial fermentation of undigested carbohydrates in the colon25, is found to be capable of inducing HDP expression in human, rabbit, chicken, and various enterocytes1626272829. Meanwhile, butyrate plays an important role in intestinalhealth242943 and has been used to treat different inflammatory disease in clinical practice30313233.…”

Organic acids in piglet nutrition – a review

“…Należą do nich peptydy przerywające błony komórkowe bakterii, takie jak protegryny oraz β-defensyny pBD-2, pBD-3 oraz pEP2C. Zastosowanie maślanu sodu zwięk-sza odporność wrodzoną i może być strategią w zwalczaniu infekcji wywołanych przez bakterie oporne na antybiotyki (45,47). Inne badania dowiodły, że maślan sodu manipulując ekspresją endogennych peptydów obronnych (przeciwdrobnoustrojowych), przyczynia się do eliminacji E. coli o sterotypie O157:H7 wywołującej zespół hemolityczno-mocznicowy.…”

“…Dodatek 2 g maśla-nu sodu na 1 kg paszy dla zainfekowanych tą bakterią prosiąt, zredukował liczbę tych patogenów w kale. To złagodziło objawy kliniczne zespołu hemolityczno--mocznicowego, a także skutki zapalenia jelit (45,47).…”