Functional analysis of gut microbial ecology using the zebrafish model system
John F. Rawls, University of North Carolina at Chapel Hill
Beginning at birth, our body surfaces are colonized by microorganisms. The majority of our microbial residents exist within dense gastrointestinal tract communities called the gut microbiota. The gut microbiota contributes to diverse aspects of our normal physiology, and has been identified as an environmental factor in diseases such as inflammatory bowel disease and obesity. Therefore, understanding the structure and function of gut microbial communities is a priority. Recent advances in DNA sequencing technology have fueled intensive analysis of gut microbial community membership and genetic potential. The resulting insights are transforming our understanding of gut microbial community structure in health and disease, and prompting important questions about gut microbiota function. What are the mechanisms underlying the assembly of gut microbial communities? What are the mechanisms utilized by gut microbes to influence host biology and pathobiology? Are these mechanisms unique to human hosts, or are they common among different vertebrate lineages? My research program is addressing these questions using the zebrafish as a host model. The small size and optical transparency of the zebrafish permit direct observation of gut microbial communities and host-microbe interactions inside a living vertebrate host. We show that host responses to the microbiota are conserved between zebrafish and mammals, despite marked differences in their respective gut microbiotas. Our results indicate that different host responses are elicited by distinct bacterial species and their products. We find that gut microbiota assembly is determined by the microbes available in the local environment, and also by selective pressures within the host. By identifying the mechanisms underlying microbial community assembly and host-microbe relationships in the gut, we hope to contribute new strategies for manipulating gut microbial ecology to promote the health of vertebrate hosts.