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Shortly after the discovery of antibiotics and their successful application to treat infectious diseases, researchers discovered the growth-promoting capacity of sub-therapeutic antibiotic treatment (Jukes and Williams, 1953; Taylor and Gordon, 1955; Dubos et al., 1963). For more than 60 yr, sub-therapeutic antibiotic treatment has been shown to increase growth rate and weight gain in a wide variety of livestock, including chickens, pigs, cows, and sheep, indicating an evolutionarily conserved relationship between microbes and host metabolism. Because of the high cost of antibiotics at the time of initial discovery (Cromwell, 2002), antibiotics were provided low levels in the animal feed. This economically constrained dosage choice turned out to be a fortunate one, since later studies demonstrated that highdose antibiotic treatment could lead to reduced weight gain or weight loss (Dubos et al., 1963; Carvalho et al., 2012). Many classes of antibiotics are efficacious for growth promotion, including those used to treat human diseases and categorized by the FDA as highly important or critically important for human health, such as b-lactams, macrolides, lincosamides, and tetracyclines (Apley et al., 2012), although the specific antibiotic within the class may differ for human vs. animal use (e.g., azithromycin is a macrolide used for humans, and tylosin a veterinary macrolide). While many antibiotics have been banned in Europe for decades (Millet and Maertens, 2011), their use is only recently being phased out in the United States in response to FDA guidance for a voluntary withdrawal. The antimicrobial dose for growth promotion is often one to two orders of magnitude lower than for therapeutic applications (Apley et al., 2012; Subbiah et al., 2016) and does not have the primary goal of treating disease or preventing infection (Allen and Stanton, 2014). For example, chlortetracycline would be administered at 70 mg/animal/day for growth promotion, at 350 mg/animal/day to for prophylaxis against catching infection, and at 22 mg/kg body weight—approximately 6,600 mg/animal for a 300-kg steer (Cazer et al., 2014). The practice of using low-dose antibiotic growth promotion continues today around the world and is projected to increase in several countries (Van Boeckel et al., 2015). While it has economic benefits associated with increasing weight gain and feed efficiency (the conversion of food to animal mass), results can vary across production facilities, and there is growing evidence and concerns that widespread use of low-dose antibiotics increases the selection for antibiotic-resistant bacteria and their transmission to the human population (Allen et al., 2013). In recent years, there has been both legislative actions and consumer pressure to reduce or eliminate the use of antibiotics for growth promotion (Borron, 2012; Antibiotics shape microbiota and weight gain across the animal kingdom