Protein discovery provides a target to treat IBD

A research team led by La Trobe University and the Olivia Newton-John Cancer Research Institute (ONJCRI) has discovered that the protein BECLIN1 appears to be integral to gut health, providing an important lead in the search for a treatment for inflammatory bowel disease (IBD). Their breakthrough has been published in the journal Communications Biology.

In a study conducted in mice, removing BECLIN1 caused problems in the internal ‘trafficking’ pathways of the epithelial cells which line the intestine, leading to a disruption of the protective barrier the cells create. This disruption can allow bacteria to enter the intestinal wall, which in turn causes the extensive inflammation associated with IBD. This is understood to be the first time BECLIN1 has been implicated as a potential factor in IBD, which includes conditions such as Crohn’s disease and ulcerative colitis.

“We have shown that removing this particular protein causes significant problems with the normal functioning and survival of the epithelial cells that line our gut and keep us healthy by fighting bacteria and ensuring nutrient absorption,” said co-lead researcher Associate Professor Erinna Lee, from La Trobe and ONJCRI.

The study also demonstrates the essential role BECLIN1 plays in endocytic trafficking, which ensures proper functioning by moving the cell’s internal elements, known as ‘cargo’, to the right place at the right time.

“This was unexpected, as BECLIN1 is best known for its involvement in another cellular process called autophagy that does have a known and strong connection with IBD,” noted co-lead researcher Associate Professor Doug Fairlie, also from La Trobe and ONJCRI.

In this study, the protein E-CADHERIN was identified as being an important cargo that relies on BECLIN1 for its correct localisation within the cell. According to Fairlie, “This makes sense, because E-CADHERIN is essential for enabling epithelial cells to stick together. If E-CADHERIN is not located correctly within the cell, then the epithelial barrier lining the gut breaks down and bacteria can penetrate the intestinal tissue, leading to a potent inflammatory response.”

Current treatments for IBD are only able to address the disease’s symptoms by reducing inflammation and treating infection, but this study could open the way for the development new treatment options. According to Lee, “We believe our discovery of BECLIN1 as a master regulator of gut health provides an important new target for further investigation into how to tackle the root causes of IBD and perhaps develop new treatments for the disease.”

Image credit: iStock.com/MarianVejcik