Regulation of intestinal homeostasis by colonic goblet cells in response to commensal and pathogenic bacteria

The gut lumen (interior space of the intestine) has developed to live in harmony with trillions of bacteria, many of which are beneficial to human health by helping in digestion and making vitamins. However, this harmony can be broken if the bacteria start to enter body tissues instead of staying in the lumenal space. Preventing this is the lining of the gut surface, which is made up of a single layer of different cells, including goblet cells. Goblet cells are single-celled mucus factories, specialized to make molecules that form a layer of mucus over the intestinal wall. While the mucus layer is believed to have a protective role, its function is not well studied in people. However, animal models that that lack mucus in the gut develop unwanted inflammatory responses and even cancer, suggesting an important function for this layer. Furthermore, defective mucus production is seen in patients with inflammatory bowel disease (IBD), which is characterized by excessive immune responses to our normally friendly bacteria. Previously funded by an MSFHR Junior Graduate Studentship award, Kirk Bergstrom is continuing his studies on how mucus-producing goblet cells promote healthy interactions with beneficial bacteria in the gut, and how they defend against harmful bacteria. He is using animal models of bacterial-driven gut inflammation, including an infection model that copies human disease. Bergstrom’s studies will shed light on how goblet cells help maintain this delicate balance within the gut. Also, since mucus production by goblet cells can be controlled by certain foods, these studies could lead the way toward new, noninvasive therapies based on nutrition to treat patients suffering from bacterial infections of the gut, or IBD.