Do goblet cell mediators co-operatively prevent gut microbiota from causing spontaneous colitis?

Inflammatory Bowel Diseases, including Crohn’s disease and ulcerative colitis are characterized by chronic intestinal inflammation and tissue damage. There are trillions of bacteria found  within the human intestine and IBDs are thought to develop when mucus barriers that normally keep these  bacteria inside the gastrointestinal tract become impaired,  allowing bacteria to escape out of the gut lumen and causing  chronic inflammation. While the role of epithelial cells in promoting barrier function is well known, the protective actions of the mucus barrier are relatively understudied.

Specialized secretory epithelial cells known as goblet cells within the gut lumen produce  mucins known as Muc2 and pro-inflammatory proteins called  RELM-ß. Through in vitro and in vivo studies, and  microbiota analysis, Morampudi plans to define how these goblet cell proteins cooperatively protect the intestine from  developing spontaneous colitis through the development of  these products.Through tests with micelacking either Muc2 or RELM-ß, Dr. Morampudi has  hypothesized that both proteins act together to protect the  intestine from gut commensal bacteria. Muc2 provides a  structural barrier, preventing bacteria from contacting the immune system, but when the mucus barrier is impaired,  RELM-ß is induced to create an antimicrobial zone above the  intestinal epithelium. Under conditions where expression of  both proteins is impaired (such as by ER stress), the  commensal bacteria are able to escape from the intestine and cause colitis/IBD.Ultimately, this research will provide insights as to how  the development of spontaneous colitis can be prevented.