Antibiotic growth promoter-induced changes in the chicken intestine: A metabolomics analysis of virginiamycin and bacitracin methylene disalicylate

Authors: GADDE, UHJVALA - US Department Of Agriculture (USDA); OH, SUNGTAEK - US Department Of Agriculture (USDA); Lillehoj, Hyun; LILLEHOJ, ERIC - University Of Maryland School Of Medicine

Submitted to: Scientific Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/5/2017
Publication Date: 4/5/2018
Citation: Gadde, U.D., Oh, S., Lillehoj, H.S., Lillehoj, E.P. 2018. Antibiotic growth promoter-induced changes in the chicken intestine: A metabolomics analysis of virginiamycin and bacitracin methylene disalicylate. Scientific Reports. 8(1):3592. https://doi.org/10.1038/s41598-018-22004-6.
DOI: https://doi.org/10.1038/s41598-018-22004-6

Interpretive Summary: Sub-therapeutic antibiotics have been used in the animal industry for more than 60 years now to improve growth performance and feed efficiency. Although the detailed mode of action of antibiotic growth promoting (AGP) drugs remains to be studied, one hypothesis indicates that antibiotics interact with host immune cells and lower the inflammatory response. Using novel molecular biology and immunology techniques, ARS scientists investigated the host- and microbiome-derived metabolite changes induced in the gut by various antibiotics compared to non-antibiotic groups on standard diets. This study showed that AGP antibiotic supplementation had profound effects on the levels of metabolites in the ileal contents of chickens which were treated with AGP drugs. Detailed analysis of these metabolite changes which is associated with host immunity upon dietary AGP treatment will lead to our enhanced understanding of the mode of action of AGP drugs.

Technical Abstract: Abstract Although dietary antibiotic growth promoters have long been used to increase growth performance in commercial food animal production, the biochemical details associated with these effects remain poorly defined. A metabolomics approach was used to characterize and identify the biochemical compounds present in the intestine of broiler chickens fed a standard, unsupplemented diet or a diet supplemented with the antibiotic growth promoters, virginiamycin or bacitracin methylene disalicylate. Compared with unsupplemented controls, the levels of 218 biochemicals were altered (156 increased, 62 decreased) in chickens given the virginiamycin-supplemented diet, while 119 were altered (96 increased, 23 decreased) with the bacitracin-supplemented diet. When compared between antibiotic-supplemented groups, 79 chemicals were altered (43 increased, 36 decreased) in virginiamycin- vs. bacitracin-supplemented chickens. The changes in the levels of intestinal biochemicals provided a distinctive biochemical signature unique to each antibiotic-supplemented group. These biochemical signatures were characterized by increases in the levels of metabolites of amino acids (e.g. 5-hydroxylysine, 2-aminoadipate, 5-hydroxyindoleaceate, 7-hydroxyindole sulfate), fatty acids (e.g. oleate/vaccenate, eicosapentaenoate, 16-hydroxypalmitate, stearate), nucleosides (e.g. inosine, N6-methyladenosine), and vitamins (e.g. nicotinamide). These results provide the framework for future studies to identify natural chemical compounds to improve poultry growth performance without the use of in-feed antibiotics. Significance Feed-additive antibiotics increase the growth of livestock and poultry, but concerns about selection for and transfer of bacterial antibiotic resistance to humans limit their use. While antibiotic growth promoters alter the metabolism of both the host gastrointestinal tract and the gut microbiome, the mechanisms responsible for their growth promoting activity are unknown. To our knowledge, the current study is the first comprehensive, global metabolomics analysis of antibiotic growth promoters used in commercial food animal production. Further analysis of the chemical compounds identified here will provide new targets to enhance food animal growth in the absence of antibiotics, thereby lessening the human risk of drug-resistant bacterial pathogens.