In-feed bacitracin methylene disalicylate modulates the turkey microbiota and metabolome in a dose-dependent manner

Beginning in 2017, the subtherapeutic use of most antibiotic compounds for growth promotion in food producing animals in the US was prohibited, highlighting the need to discover alternative growth promotants. Identifying the mechanism of action of growth promoting antibiotics may aid in the discovery of antibiotic alternatives. We describe the effects of feeding a subtherapeutic (50 g/ton of feed) and therapeutic (200 g/ton) concentration of bacitracin methylene disalicylate (BMD) to commercial turkeys for 14 weeks, and its effect on turkey intestinal microbial communities and cecal metabolomes. Both BMD concentrations had an immediate and lasting impact on the microbiota structure, and reduced bacterial richness through the end of the study (12 weeks). Metabolomic analysis identified 712 biochemicals, and 69% of metabolites were differentially present in BMD treated turkeys for at least one time point (q < 0.1). Amino acids, carbohydrates, nucleotides, peptides, and lipids were decreased in the turkey ceca early after BMD administration. Long-term metabolome alterations continued even after withdrawal of BMD. The microbial composition, determined by 16S rRNA gene sequencing, was predictive of the metabolome, indicating a connection between the microbiome and metabolome. In-feed BMD may cause bacterial metabolic shifts, leading to beneficial traits that can be targeted to improve animal health and production.