In collaboration with the Teratology Society, British Toxicology Society, and Society of Toxicologic Pathology, the American College of Toxicology presented a webinar on the Influence of the Microbiota in Drug Development and Preclinical Studies on Wednesday, August 24, 2016.
A recording of this webinar is now available to Teratology Society members in the Educational Webinars File Library.
Aaron C. Ericsson, DVM, PhD, Research Assistant Professor; Department of Veterinary Pathobiology; Director, University of Missouri Metagenomics Center
Julia Yue Cui, PhD, Assistant Professor, Department of Environmental and Occupational Health Sciences, University of Washington
The host-associated microbiota has a profound role in human health and disease susceptibility. Host microbiota has a strong influence on the phenotype of many animal models and should be considered during the study design and data interpretation. Many common variables associated with animal husbandry can greatly influence the composition of the gut microbiota and potentially impact the study outcomes. Moreover, organ systems colonized by their own cognate microbiota have implications for the development of specific organ-targeted compounds. The first part of the webinar will focus on the implications of gut microbiota on animal model development, including the influence of standard practices on study reproducibility and translatability to human health and disease.
The critical role of intestinal bacteria on the host intermediary metabolism including obesity and type II diabetes are well known. Relatively less known is the impact of intestinal bacteria on the hepatic expression of various drug-metabolizing enzymes and transporters as well as the hepatic metabolism of xenobiotics. Germ-free mice and second- generation sequencing technology have been employed to determine the impact of alterations in gut microbiome on the hepatic drug-processing gene expression and xenobiotic metabolism. The presence of intestinal microbiota during liver development markedly impacted the normal ontogeny of many hepatic drug-processing genes. Additionally, introducing exogenous bacteria by probiotics or conventionalization influenced the hepatic drug-processing capacity. Finally, environmental chemical-mediated alterations in many hepatic drug-processing genes depended on the presence of a normal configuration of the gut microbiome. The second part of the webinar will focus on the critical impact of gut microbiota on the gene expression of drug-metabolizing enzymes and the xenobiotic metabolism by the host liver with specific examples.