Ecological drivers of gut microbiome and antimicrobial resistance in swine

Abstract

The pig gastrointestinal tract hosts a large and diverse microbial community, representing a complex and dynamic ecosystem. The microbial communities are not uniformly distributed and differ across the locations of the gastrointestinal tract. The microbial community composition influences the prevalence and distribution of antimicrobial resistance (AMR) in the gut. The microbial taxonomic composition, richness, and diversity are influenced by age of the pig, dietary composition, and antimicrobial drug use. The association between antimicrobial use and AMR development is of interest because of public health implications. Several studies in swine and cattle have reported a decrease in AMR in fecal bacteria with animal age; however, exact dynamics and contributing factors are largely unknown. Investigations on the AMR dynamics in gut microbiome during the production phase of food animals could aid in the design of a framework to address the problem of AMR in the food chain in a sustainable manner. The primary hypothesis of our study was that the dynamics of gut microbiome and AMR in swine are largely a function of age and dietary composition. Therefore, the objectives of the studies were: 1. Perform a scoping review of the literature on the age-dependence of AMR of fecal bacteria in food animals. 2. Conduct longitudinal studies to evaluate the dynamics of fecal bacteriome and mycobiome taxonomic compositions and AMR prevalence between cohorts of production pigs (n=12) from birth to harvest and breeding sows (two cohorts, n=6 and n=12) from 3 weeks through first farrowing and weaning, to test the hypothesis that the dynamics are a function of age, rather than the production system. 3. Investigate interactions between the age-related dynamics and effects of diet (levels and sources of fiber) and antimicrobial treatments (injectable ceftiofur or penicillin G) in influencing the fecal microbiome taxonomic composition and AMR in finisher pigs. 4. Conduct a study to describe bacterial community composition associated with luminal contents and mucosal epithelium from different segments of the gut of piglets. Culture-based and metagenomic analyses coupled with statistical modeling were utilized to monitor microbiome changes and estimate and infer AMR occurrence in gut bacterial communities in relation to age and diet. The scoping review of published data suggested that the animal-level prevalence and within-animal abundance of AMR in enteric or fecal bacteria decreased with age during the production life-span in pigs, in beef and dairy cattle. The age-dependent dynamics of fecal bacteriome and mycobiome taxonomic compositions and associated animal-level prevalence and within-animal abundance of AMR were similar in a cohort of production pigs and two cohorts of breeding sows. The highest AMR prevalence and abundance occurred at the youngest age-points and decreased with age and stabilized around 5 to 6 months of age. The data suggested a strong age-dependence and additional independent diet effects on the fecal microbiome composition and AMR. Data also showed that the concentrations of ceftiofur metabolites in swine feces were lower on day 3 compared to day 1 of the 3-day ceftiofur treatment, irrespective of the animal diet or gender. In a study conducted in piglets (6-7 weeks old: n=3), luminal contents and mucosa were collected from the stomach, duodenum, ileum (at two locations), cecum, spiral colon, and the rectum. The bacterial community composition and AMR genes were determined, and the study showed that the bacterial taxonomic composition and AMR gene repertoire changed throughout the gastrointestinal tract of piglets. Genes encoding bacterial resistance or reduced susceptibility to tetracyclines, β-lactams, aminoglycosides, and glycopeptides were most abundant AMR genes in the samples. In summary, age and diet, in addition to the use of antimicrobials, play an important role in the establishment and maintenance of gut microbial diversity and AMR in pigs.