Dietary Antibiotic Growth Promoters Down-Regulate Intestinal Inflammatory Cytokine Expression in Chickens Challenged With LPS or Co-infected With Eimeria maxima and Clostridium perfringens.

Sungtaek Oh,Erik P Lillehoj,Youngsub Lee,David Bravo,Hyun S Lillehoj

doi:10.3389/fvets.2019.00420

Abstract

Subtherapeutic levels of dietary antibiotics increase growth performance in domestic animals, but the mechanisms are poorly understood. Here, 1-week-old broiler chickens were challenged with LPS (experiment 1), or co-infected with Eimeria maxima and Clostridium perfringens as an experimental model of necrotic enteritis (experiment 2), and fed a standard basal diet or a basal diet supplemented with virginiamycin or bacitracin methylene disalicylate. In experiment 1, LPS-challenged chickens fed the unsupplemented diet had decreased body weight gains, compared with unsupplemented controls given the PBS control. In contrast, antibiotic supplementation increased body weight gains in both the LPS-challenged and PBS groups, compared with the antibiotic-free diet. LPS-challenged chickens fed the unsupplemented diet had increased expression levels of intestinal tight junction proteins (ZO1, JAM2), MUC2 gel-forming mucin, and inflammatory cytokines (IL-1β, IL-2, IL-6, IL-8, IL-17A) at 24 h post-challenge, compared with unsupplemented chickens given the PBS control. However, LPS-challenged chickens fed the antibiotic-supplemented diets had decreased levels of intestinal inflammatory cytokine transcripts, compared with LPS-challenged chickens given the unsupplemented basal diet. In experiment 2, E. maxima/C. perfringens-co-infected chickens fed the antibiotic-supplemented diets had increased body weight gains, decreased intestinal pathology, and greater intestinal crypt depth, compared with co-infected chickens given the unsupplemented diet. Further, similar to LPS challenge, E. maxima/C. perfringens-co-infection of chickens fed the antibiotic-supplemented diets decreased expression levels of intestinal inflammatory cytokines, compared with co-infected chickens given the unsupplemented diet. These results support the hypothesis that dietary antibiotic growth promoters might increase poultry growth, in part, through down-regulation of pathogen-induced inflammatory responses.

Highlights

The first report of antibiotics as animal growth promoters was published in 1946 [1]
We previously reported that virginiamycin and bacitracin methylene disalicylate, two commonly-used antibiotic growth promoters (AGPs) in commercial poultry production, alter the intestinal metabolome in naïve chickens [21]
The current study was conducted to elucidate the potential mechanism through which the AGPs, virginiamycin and bacitracin methylene disalicylate, might increase poultry growth performance under conditions simulating exposure to infectious pathogens

Summary

Introduction

The first report of antibiotics as animal growth promoters was published in 1946 [1]. In the subsequent 70 years, antibiotic growth promoters (AGPs) have been commercialized as nontherapeutic dietary supplements to improv food animal growth and feed conversion efficiency, prevent infectious diseases, and maximize economic profits [2]. More recent efforts have focused on reducing or eliminating AGP use with the realization that overuse of AGPs in agricultural animals leads to the development of antibiotic resistant bacteria with the potential to spread to the human population [3, 4]. The U.S Food and Drug Administration has requested that pharmaceutical companies voluntarily discontinue labeling antimicrobials for growth promotion in agricultural animals, and antibiotics should only be prescribed for therapeutic uses through veterinary oversight [6]. Among the new initiatives to eliminate AGP use in food animals is the development of alternatives to antibiotics that improve growth performance while maintaining optimal animal health. Some of the alternatives that have been described are probiotics, prebiotics, synbiotics, organic acids, enzymes, and phytochemicals [7]

Objectives

Methods

Results

Conclusion