With increasing pressure to reduce the use of conventional antibiotics in livestock production systems, high-dose zinc therapy has become a popular alternative, but there is insufficient research assessing its risk to the health of animals, humans, and the environment. The objectives of this investigation were: (i) to determine whether zinc could inadvertently co-select for antibiotic-resistance given the co-location of the zinc-resistance gene (czrC) within a bacterial resistance island, and (ii) to better understand the early-life porcine microbiota and to determine whether zinc impacts the bacterial ecology of the porcine nasal microbiota. First, epidemiological and experimental studies were conducted to determine the effects of zinc on the co-selection of antibiotic-resistance genes in methicillin-resistant Staphylococcus aureus (MRSA) which is commonly carried by pigs and is a potential risk to public health. These studies revealed that exposure to high doses of in-feed zinc can affect the prevalence and persistence within a nursery pig herd and that the presence of MRSA on farms is strongly associated with the use of zinc therapy in nursery diets. Second, the porcine nasal and fecal microbiotas were studied using next-generation sequencing. Under normal conditions, pigs have a very rich and diverse microbiota which undergoes a rapid evolution during the first several weeks of life. When given zinc therapy, the nasal microbiota demonstrated an increased richness of bacteria, greater relative abundance of uncommon bacterial taxa, and a less established core microbiota comprised of only a highly zinc-resistant bacterial genus. These findings suggest that zinc therapy may increase susceptibility to additional bacteria beyond what is normally observed among the nasal microbiota; although, it cannot be said whether this has positive or negative implications for host health. The use of a therapeutic zinc diet in swine production systems appears to be associated with the co-selection of livestock-associated MRSA. Evidence also suggests that zinc therapy may increase the susceptibility of the nasal microbiota to colonization with zinc-resistant bacterial species, such as livestock-associated MRSA. In conclusion, zinc therapy appears to be at least one factor that is driving the emergence and persistence of MRSA in commercial swine herds.