Barcelona, 26 October, 2022.- Ulcerative colitis is the most common type of inflammatory bowel disease, characterised by chronic ulcers and inflammation in the colon and rectum. Symptoms can be lifelong and range from mild to life-threatening. There is no known cure for this human pathology.

Researchers have suspected that a malfunctioning immune system, where immune cells attack the epithelial cells in the colon, could explain the recurring bouts of inflammation that are characteristic of the disease. However, what makes the immune system attack healthy cells in the first place remains a mystery.

A new study published in the Proceedings of the National Academy of Sciences proposes a set of conditions that could act as a starting point for the development of ulcerative colitis. Using a combination of experimental data from patient biopsies, mouse models and cell lines, researchers show the disease may be caused because of increasing levels of the enzyme alpha 1-6 fucosyltransferase – also known as FUT8 – in the colon. Levels of this enzyme are normally low in healthy individuals.

FUT8’s main function is to modify the physical properties of many different types of proteins through a process known as fucosylation. In 2016, research led by Dr. Naoyuki Taniguchi from the Osaka International Cancer Institute showed that mice which lacked FUT8 were protected from ulcerative colitis, but it was unclear why. This caught the attention of Vivek Malhotra’s research group at the Centre for Genomic Regulation (CRG) in Barcelona, who back in 2013 had found that FUT8 could play a role in the secretion of mucins, proteins that form the major component of the mucous layer. The researchers decided to work together to further elucidate the role of FUT8 in ulcerative colitis.

Mucins are large proteins that swell several hundred times in volume upon their release into the extra cellular space. It is estimated that humans secrete an average of one litre of mucins per day, which combine with other molecules to create mucous – a thick, slippery liquid that coats, lubricates and protects the entire gastrointestinal tract, a surface area that is roughly half the size of a badminton court.

The researchers collaborated with the CNAG-CRG’s Biomedical Genomics group led by Ivo Gut, who provided gene expression data collected from the biopsies of colonic tissue from 24 patients with ulcerative colitis and the same type of tissue from 16 healthy patients. This revealed that FUT8 levels were 3.5 times higher in samples of patients with ulcerative colitis compared to those without the condition. They also found that levels of several types of mucins were increased in the inflamed colon of ulcerative colitis patients.

More information on the CRG website

Work of reference

The ulcerative colitis-associated gene FUT8 regulates thequantity and quality of secreted mucins