Abstract

The changes in the gut microbiome play an important role in the promoting effects of antibiotics, such as tylosin, to the health, and productivity of farm animals. Microbial metabolites are expected to be key mediators between antibiotics-induced microbiome changes and growth-promoting effects. The objective of this study was to extend the identification of tylosin-responsive microbes to the identification of tylosin-responsive metabolites in growing pigs. The feeding trial was conducted on a commercial farm using two pens of pigs fed diets with and without tylosin (40 mg/kg of diet). Fecal samples were collected from 10 pigs per pen at weeks 10, 13, 16, 19, and 22 of age, and subsequently analyzed using liquid chromatography-mass spectrometry (LC-MS) analysis. The multivariate model of LC-MS data showed that time-dependent changes occurred in the fecal metabolome of both control and tylosin-treated pigs. More importantly, the metabolomic profiles were similar between the tylosin treatment and control groups in weeks 10 and 22, but diverged during weeks 13–19. Subsequent analyses of the fecal metabolites contributing to the separation of two groups of pigs showed that hyodeoxycholic acid (HDCA), together with tylosin and its metabolites in feces, was greatly increased during weeks 13–19 (P < 0.05) in the group of pigs fed tylosin. The integration of current metabolomics data and the microbiome data from a previous study revealed the consistency between HDCA and a specific genus of microbes in the Clostridia family. Further studies are required to determine the causative relations between tylosin-elicited changes in HDCA and the microbiome as well as the role of HDCA in the growth promoting effects of tylosin.

Highlights

  • IntroductionCurrent food animal production systems have been able to supply animal products (e.g., milk, eggs, meat) at lower cost than ever before

  • Current food animal production systems have been able to supply animal products at lower cost than ever before

  • Because metabolites can function as energy carriers and signaling initiators of the growth and wellbeing of host and gut microbes, metabolomic analysis could provide useful insights on the connections between growth promoting effects and microbiome modulating effects of antibiotics

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Summary

Introduction

Current food animal production systems have been able to supply animal products (e.g., milk, eggs, meat) at lower cost than ever before. Efficiency of food animal production is greater in modern production systems than in the past, while decreasing environmental impact [1]. Modern farms attained such efficiencies in productivity in part because of the implementation of technologies such as utilization of antibiotics as growth promoters. The use of antibiotics increases selective pressures responsible for the evolution of antibiotic resistant bacteria [4, 5]. The One Health framework suggests that animal health is closely linked to human health and the use of antibiotic growth promoters increases the risk of antibiotic resistant bacteria in humans [6]. It is necessary to develop strategies that maintain and improve animal productivity while reducing the usage of antibiotics in the production of livestock

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