How do intestinal microbiota interact with host genome-encoded processes to impact vertebrate health and disease?
Animal physiology is directed by complex interactions between factors encoded in the animal’s genome and those encountered in their environment. The impact of these interactions on animal health is most evident in the intestine, where digestion and absorption of dietary nutrients occur in the presence of complex communities of microorganisms (microbiota). Interactions between diet, microbiota, and animal hosts regulate immune and metabolic homeostasis and also contribute to a spectrum of human diseases, including the inflammatory bowel diseases, obesity, and malnutrition. Our research interests are focused on understanding how environmental factors such as the intestinal microbiota and diet interact with host genome-encoded processes to influence host physiology and pathophysiology. We are using the zebrafish as a vertebrate model system for this research. The small size and optical transparency of the zebrafish facilitate high-resolution in vivo imaging as well as genetic and chemical manipulations that complement the technical limitations of mammalian models. Extensive anatomic, physiologic, and genomic homologies between zebrafish and mammals permit translation of insights gained in zebrafish into advances in human medicine. To facilitate our research, we have developed methods for rearing zebrafish under germ-free conditions and for introducing selected microbial communities and sterilized diets into germ-free fish. We are currently using zebrafish and mouse models to investigate how microbial communities are assembled in the intestine and how microbes and dietary nutrients regulate host metabolism and immunity. We have also established methods for in vivo analysis of adipose tissues in zebrafish, and we are using that experimental platform to elucidate the mechanisms underlying adipose tissue physiology and obesity-associated metabolic disease. The overall objective of our work is to improve our understanding of vertebrate physiology as a complex and dynamic integration of genome-encoded and environmental factors, which is expected to yield new strategies for promoting health in humans and other animals.