Could a Swimming Creature Inform Us on Intestinal Diseases? Lessons from Zebrafish

Understanding a complex pathology such as inflammatory bowel disease, where host genetics (innate and adaptive immunity, barrier function) and environmental factors (microbes, diet, and stress) interact together to influence disease onset and severity, requires multipronged approaches to model these numerous variables. Researchers have typically relied on preclinical models of mouse and rat origin to push the boundary of knowledge further. However, incorporation of novel vertebrate models may contribute to new knowledge on specific aspects of intestinal homeostasis. An emerging literature has seen the use of zebrafish as a novel animal system to study key aspects of host–microbe interactions in the intestine. In this review, we briefly introduce components of host–microbiota interplay in the developing zebrafish intestine and summarize key lessons learned from this animal system; review important chemically induced and genetically engineered zebrafish models of intestinal immune disorders; and discuss perspectives and limitations of the zebrafish model system