Inflammatory Bowel Disease (IBD) affects roughly 1.6 million people in the USA alone, and was first described in 1932. Nevertheless, science has only scratched the surface of the mechanisms that decide how the disease begins and why some people develop IBD and others don’t. It’s well known that there is a genetic element to IBD, although we don’t know why certain types of genes sensitise people to IBD. Now, a new study has connected the dots between one gene variant and the symptoms of IBD, potentially paving the way for therapies targeting these symptoms.
The study, published this week in Science, examined a gene variant called C1orf106. The study’s authors, a collaborative group from MIT, Harvard, the Montreal Heart Institute Research Center, Massachusetts General Hospital and Université de Montréal, noticed that C1orf106 interacted with various proteins that regulate processes in the gut. They focused in on one of these proteins, called CYTH1. Through binding to CYTH1, C1orf106 controls how much of the protein is produced and in what form it is produced.
CYTH1 has a key function in the gut – to recycle old proteins from the gut lining after they are damaged. The C1orf106 gene variant reduced the success that CYTH1 has in recycling these proteins, meaning more old, faulty proteins accumulate in the lining of the gut, leading to the characteristic inflammation of IBD.
As IBD progresses, the gut lining inflammation means it loses its ability to absorb water from waste passing through it, leading to diarrhoea. Abdominal cramping, weight loss and fatigue are some of the other symptoms of IBD. The disease is split into two rough categories depending on the location and type of inflammation – Ulcerative Colitis and Crohn’s Disease.
What this research means is that scientists can now start targeting this protein as a possible therapeutic option for IBD treatment. Dr Kara Lassen, who co-authored the study, commented on the findings’ potential, and the route between this work and a treatment for IBD: “This work reinforces the concept that drugs aimed at strengthening the gut barrier could be combined with drugs that suppress the immune system to restore balance in the gut and help patients achieve remission. The next step would be to design such therapies that enhance the barrier. It is likely that there are many subtle changes in people that alter how this barrier is formed so the obstacle is how to find such therapies since this pathway is tightly regulated. Also, the gut epithelial barrier must be tight enough to prevent bacteria from passing through but loose enough to allow the passage of nutrients and other solutes. Ideally we can find a therapeutic that can mimic this balance.”
Reference: Mohanan, V., Nakata, T., Desch, A. N., Lévesque, C., Boroughs, A., Guzman, G., … Xavier, R. J. (2018). C1orf106 is a colitis risk gene that regulates stability of epithelial adherens junctions. Science. https://doi.org/10.1126/science.aan0814