Dietary antibiotic growth promoters down-regulate inflammatory cytokine expression in chickens challenged with LPS or co-infected with Eimeria maxima and Clostridium perfringens

Authors: OH, SUNGTAEK - US Department Of Agriculture (USDA); Lillehoj, Hyun; LEE, YOUNGSUB - US Department Of Agriculture (USDA); BRAVO, DAVID - Land O'Lakes, Inc; LILLEHOJ, ERIK - University Of Maryland School Of Medicine

Submitted to: PLOS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/7/2019
Publication Date: 11/22/2019
Citation: Oh, S., Lillehoj, H.S., Lee, Y., Bravo, D., Lillehoj, E.P. 2019. Dietary antibiotic growth promoters down-regulate inflammatory cytokine expression in chickens challenged with LPS or co-infected with Eimeria maxima and Clostridium perfringens. PLoS One. https://doi.org/10.3389/fvets.2019.00420.
DOI: https://doi.org/10.3389/fvets.2019.00420

Interpretive Summary: Since the antibiotic growth promoters (AGPs) have been commercialized as nontherapeutic dietary supplements to improve food animal growth and feed conversion efficiency, prevent infectious diseases, and maximize economic profits in 1950, availability of AGPs made major contribution to the growth of agricultural animal industry worldwide. However, with increasing governmental restriction of AGPs, 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. In this report, ARS scientists in collaboration with scientists from University of Maryland and a private food industry conducted detailed studies to investigate a comprehensive understanding of the biological mechanism of action of AGPs is need in order to develop effective non-antibiotic alternatives that retain their growth enhancing properties without promoting antimicrobial resistance. Using two commonly-used AGPs in commercial poultry production, virginiamycin and bacitracin methylene disalicylate, results showed that sub therapeutic levels of dietary antibiotics increased body weight gains in both the LPS-challenged and PBS groups, compared with the antibiotic-free diet. Furthermore, LPS-challenged chickens fed the antibiotic-supplemented diets had decreased levels of intestinal inflammatory cytokine transcripts, compared with co-infected chickens given the unsupplemented diet. Taken together with previous reports from ARS laboratory, the current study show scientific evidence to suggests that dietary AGPs increase poultry growth, in part, through down-regulation of pathogen-induced, cytokine-mediated inflammatory responses. This report should provide important information that will lead to the development of effective antibiotic alternatives.

Technical Abstract: Sub therapeutic levels of dietary antibiotics increase growth performance in commercial food animals, but the mechanisms are poorly understood. Here, 1-week-old broiler chickens were challenged with LPS, or co-infected with Eimeria maxima and Clostridium perfringens as an experimental model of necrotic enteritis, and fed a standard basal diet or a basal diet supplemented with virginiamycin or bacitracin methylene disalicylate. LPS-challenged chickens fed the unsupplemented diet had decreased body weight gains, compared with un-supplemented controls given the PBS vehicle alone. 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 levels of intestinal transcripts encoding intercellular tight junction proteins (ZO1, JAM2), the MUC2 gel-forming mucin, and inflammatory cytokines (IL-1ß, IL-2, IL-6, IL-8, IL-17A) at 24 hr. post-challenge, compared with un-supplemented 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 un-supplemented basal diet. 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 the levels of intestinal transcripts encoding 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.