Grant: Project Grant

Normal function of the digestive system is key to good health. During digestion, food moves from the stomach to the small intestine, where absorption of nutrients occurs, and finally to the colon for elimination. Not only does the gut move and digest food, but while doing so it must protect the rest of the body from ingested pathogens, food antigens and from the microbes that live in its lumen. These microbes are essential for health, but must remain in the intestine or they can cause harm. Thus the gut has a dual role: digestion and defense. Digestion and defense are sufficiently complex that a "brain" is required to regulate and control them. This brain in the gut is called the enteric nervous system (ENS). The ENS is composed of nerves and specialized cells called enteric glial cells. Enteric glial cells were originally thought to be passive support cells, but through our research we know that nerves and glial cells actively communicate with each other by releasing chemical messengers. This bi-directional nerve-glial communication is important for the ENS to control the movement of food through the gut and for defense. We have recently shown that defects in enteric glia contribute to a reduction in the defensive functions of the inflamed gut. When we reversed these defects, the inflammation (colitis) was much improved. The goal of the project is to establish the role of enteric glia in the control of gut barrier function; a key component of defense. Our objectives are to show how these cells interact with other signaling systems in the gut to regulate the gut barrier in health and disease. We expect to show that enteric glia will regulate gut barrier function and that we can selectively manipulate glial signaling pathways to enhance barrier function and limit gastrointestinal disease. These studies will advance health-related knowledge and lead to new treatments for debilitating gastrointestinal disorders such as inflammatory bowel disease.