275 Awardee Talk: Gnotobiotic Porcine Models to Better Understand Gut Microbiome-Host Interactions in Human and Porcine Hosts

Abstract

Abstract Better understanding the interactions between the gut microbiome and its host is at the forefront of research conducted in areas related to human health as well as livestock production. The complexity of the gut microbiome as well as the numerous environmental and host factors that influence the structure and function of the microbial community complicates the study of host-gut microbiome interactions under natural conditions. To this end, germ-free animal models which have been transplanted with target microbiomes and raised under controlled experimental conditions provide a unique opportunity to mitigate some of the inherent difficulties related to studying host-microbiome interactions in conventional animals as well as in humans. Due to its high degree of similarity to humans at the anatomical, biochemical, and immunological levels and its importance in the livestock industry, the domestic pig (Sus scrofa domesticus) is an excellent animal model which has a unique ‘dual-purpose’ potential for use in both human health and livestock production research. Using high-throughput DNA sequencing technologies, we have demonstrated some of the advantages of using human microbiota-associated (HMA) porcine models compared with commonly used HMA mouse models to study the human gut microbiome. Specifically, we identified that a significantly greater percentage of taxa from child, adult, and senior donors were able to colonize (69% to 85% in pigs versus 41% to 49% in mice) and persist (28% to 57% in piglets versus 21% to 28% in mice) in the HMA piglets compared with the HMA mice, and that this was primarily driven by a greater colonization success of Firmicutes members in the pigs compared with the mice. In addition, we have characterized human infant microbiota-associated porcine models at both the taxonomic and functional levels to better understand the HMA piglet as a model for infant microbiome investigations. We have also utilized the porcine microbiota-associated (PMA) pig model to understand the establishment and development of the porcine gut microbiome. This model has great potential to dissect the mechanistic relationship between the host and its microbiome in pigs. Additionally, this model can be used to understand how prebiotics and direct-fed microbials might interact with the gut microbiome and influence porcine health and well-being. Despite some of the challenges to the widespread use of gnotobiotic porcine models, such as high overhead costs and labor involved in animal care, the porcine model holds a lot of promise to help better understand host-gut microbiome interactions.