Research Article: Evaluating nursery pig responses to in-feed sub-therapeutic antibiotics

Date Published: April 26, 2019

Publisher: Public Library of Science

Author(s): Emma T. Helm, Shelby Curry, Julian M. Trachsel, Martine Schroyen, Nicholas K. Gabler, Juan J. Loor.


Antibiotics have been used for over 60 years by the swine industry to improve growth performance and feed efficiency. With rising concerns over antimicrobial resistance and government restrictions such as the Veterinary Feed Directive on usage of in-feed antibiotics, alternatives to feeding antibiotic growth promoters (AGPs) to nursery pigs are needed. However, the mechanism of action by which AGPs work is poorly understood. Thus, the objective of this study was to investigate the mechanisms of action by which AGPs increase nursery pig performance. Over two replicates, 24 weaned pigs (6.75 ± 0.75 kg body weight) were randomly allotted to either control (CON, n = 12) or sub-therapeutic antibiotic (sCTC, n = 12) treatments and housed individually. A 2-phase corn-soybean-based nursery diet was fed, with the sCTC diets containing 40 ppm feed-grade chlortetracycline. Individual pig average daily gain (ADG), average daily feed intake (ADFI), and gain to feed ratio (G:F) were calculated weekly for 5 weeks. Thereafter, all pigs were euthanized and necropsied for tissue collection. The overall performance data indicated that sCTC pigs had increased ADG (0.43 vs. 0.32 kg/d, P = 0.001) and ADFI (0.51 vs. 0.37 kg/d, P = 0.002) compared with CON pigs; however, G:F was not different as a result of dietary treatment (0.85 vs. 0.88, P = 0.617). Intestinal barrier permeability, ileal active nutrient transport, and cecal short chain fatty acid concentrations did not differ (P > 0.10) due to dietary treatment, however changes in several ileum mRNA transcripts suggest that inflammation may be reduced in sCTC pigs. Further, the changes observed in the proteomes of the ileum, colon, skeletal muscle, and liver suggest that the sub-therapeutic mode of action of AGPs may include post-absorptive changes and warrants further investigation.

Partial Text

Sub-therapeutic antibiotic growth promotants (AGPs) have been used heavily by the swine industry since their growth promoting qualities were first discovered in the 1940s [1]. Antibiotic growth promotants have been shown to consistently improve body weight gain and feed efficiency in growing pigs, specifically during the nursery phase [2]. However, rising concerns over antimicrobial resistance to antibiotics has resulted in the United States animal agriculture sector banning the use of sub-therapeutic growth promoting antibiotics via the recent implementation of the 2017 Veterinary Feed Directive (VFD) [3]. The VFD prohibits the usage of sub-therapeutic AGPs, which can be defined an antimicrobial fed at concentrations lower than the lowest concentration that will inhibit the growth of the target microorganism of that antimicrobial. One of the most commonly used AGPs has been chlortetracycline (CTC) [4]. The potential of tetracycline antibiotics to promote growth was first shown in the 1940s when healthy animals that consumed dried mycelia of Streptomyces aureofaciens containing chlortetracycline residues were observed to have improved growth [5]. The tetracycline class of antibiotics exert their effect on Gram-positive, and to a lesser extent, Gram-negative bacteria by binding to the bacterial 30S and 50S ribosome and halting protein synthesis [6, 7]. In hosts, tetracyclines have also been shown to act as reactive oxygen species scavengers or anti-inflammatory agents, to inhibit matrix metalloproteinases, and to possess anti-apoptotic properties [6]. Tetracycline antibiotics have been used both therapeutically and sub-therapeutically in animal agriculture. In-feed therapeutic levels of CTC have historically been 400 ppm or greater [8]. For use as an in-feed sub-therapeutic AGP, CTC has been added at low concentrations (2.5 ppm to 125 ppm), depending upon both the animal species and the drug type, to enhance animal performance as opposed to treating, controlling, and preventing disease [9, 10].

All animal procedures in this study were approved by the Iowa State University Institutional Animal Care and Use Committee (protocol number 4-16-8251-S) and adhered to the ethical and humane use of animals for research.

Sub-therapeutic levels of tetracyclines have been widely used in animal agriculture, largely due to their ability to consistently improve growth performance [2]. In the current study, ADG was improved 26% by sCTC (40 ppm), which is a larger increase than what is typically observed in a research setting [17–19]. Interestingly, feed efficiency did not differ in the current study, which differs from much of the historical literature demonstrating that antibiotics improve feed efficiency [19]. However, much of this historical research demonstrating feed efficiency differences is rather old or uses therapeutic doses of antibiotics. The lack of feed efficiency improvement is consistent with more recent observations by Shen et al. [18] using sub-therapeutic CTC. Thus, the lack of feed efficiency differences in the current experiment may be due to more modern pig genetics, more sanitary housing conditions, or the dose of CTC utilized. Further, sCTC pigs were 4 kg heavier than CON pigs at the end of the study, re-emphasizing the impact sub-therapeutic levels of antibiotics can have on nursery pig growth performance and producer economic returns. However, due to consumer and government concerns regarding increasing antimicrobial resistance, AGPs are being phased out of use by production animal agriculture [3, 20]. With the loss of such a crucial production tool, the swine industry has raced to develop alternatives that mimic the growth promoting benefits of AGPs without the risk of increasing antimicrobial resistance. However, despite their heavy usage by the industry for over 50 years, the mode of action by which AGPs improve growth performance is still unclear. Most research that has investigated the impact of CTC on pig growth, metabolism, and microbiota has utilized a therapeutic dose of 400 ppm or greater [21–23], which is 10 times greater than the sub-therapeutic dose used in the industry and likely has different effects on the pig and intestinal microbiota. Thus, this experiment aimed to investigate the mode of sub-therapeutic, rather than therapeutic, concentrations of CTC on pig growth and metabolism.




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