Human Microbiota-Associated Swine: Current Progress and Future Opportunities

Gnotobiotic (GN) rodent models have provided insight into the contributions of the gut microbiota to host health and preventing disease. However, rodent models are limited by several important physiological and metabolic differences from humans, and many rodent models do not dependably replicate the clinical manifestations of human diseases. Due to the high degree of similarity in anatomy, physiology, immunology and brain growth, the domestic pig (Sus scrofa) is considered a clinically relevant model to study factors influencing human gastrointestinal, immune, and brain development. Gnotobiotic piglet models have been developed and shown to recapitulate key aspects of GN rodent models. Human microbiota-associated (HMA) piglets have been established using inocula from infants, children, and adults. The gut microbiota of recipient HMA piglets was more similar to that of the human donor than that of conventionally reared piglets harboring a pig microbiota. Moreover, Bifidobacterium and Bacteroides, two predominant bacterial groups of infant gut, were successfully established in the HMA piglets. Thus, the HMA pig model has the potential to be a valuable model for investigating how the gut microbiota composition changes in response to environmental factors, such as age, diet, vaccination, antibiotic use and infection. The HMA also represents a robust model for screening the efficacy of pre- and probiotic interventions. Lastly, HMA piglets can be an ideal model with which to elucidate microbe-host interactions in human health and disease due to the similarities to humans in anatomy, physiology, developmental maturity at birth, and the pathophysiology of many human diseases.