- Ulcerative colitis is a chronic inflammatory bowel disease that can cause severe symptoms, such as abdominal pain, bloody diarrhea, and weight loss.
- People with ulcerative colitis experience flare-ups and periods of remission. Current treatments can alleviate but not cure the condition.
- A new study suggests that a simple stool test could identify the condition in its early stages by detecting changes in mucus.
Ulcerative colitis (UC) is a relatively common bowel disease where inflammation and ulcers in the large intestine lead to abdominal pain and bloody diarrhea. The condition can also cause tiredness, weight loss, loss of appetite, and anemia.
Experts have not yet identified the exact cause of UC, which most commonly develops between the ages of 30 and 40. It is thought that genes, abnormal immune reactions, the microbiome, and the environment may all play a part.
Dr. Harry Thomas, a board certified gastroenterologist at Austin Gastroenterology, told Medical News Today:
“Ulcerative colitis is a chronic inflammatory bowel disease, resulting in diarrhea and rectal bleeding. The factors that lead to the development of ulcerative colitis are complex and not fully understood, but clearly include some combination of genetic susceptibility, environmental triggers, immune system abnormalities, altered composition of the gut microbiome, and compromise of the intestinal epithelial barrier.”
Most people with the condition experience flare-ups with symptom-free periods between. Medications and lifestyle changes can help prevent and manage flare-ups, so early diagnosis is key to managing the condition.
Currently, diagnosis of UC is made by endoscopy and biopsy.
“Ulcerative colitis is typically diagnosed by colonoscopy with biopsies, which is an invasive procedure requiring bowel preparation and usually sedation. There are noninvasive tests available that can provide clues to the diagnosis of ulcerative colitis, including both blood tests and stool tests; however, these are nonspecific and can also be elevated in other conditions that result in intestinal inflammation.”
— Dr. Harry Thomas
Now, new research, published in Proceedings of the National Academy of Sciences, suggests that testing stool samples to detect altered mucus might be an accurate, noninvasive method for diagnosing UC early.
Altered enzyme levels in the colon
The researchers used a combination of experimental data from patient biopsies, mouse models, and cell lines to investigate the causes of UC.
They found that patients with the condition had much higher than expected levels of a particular enzyme — alpha 1-6 fucosyltransferase (also called FUT8) — in their colons. In healthy people, levels of FUT8 are very low.
FUT8 changes the composition of mucins, proteins that form the layer of mucus in the large intestine, through a process called fucosylation.
In this study, the researchers found that people with UC had levels of FUT8 that were 3.5 times higher than those of healthy patients. They also had increased levels of several different mucins.
Mucous layer changes
The mucous layer in the large intestine protects it from inflammation and infection, forming a barrier to bacteria.
In mouse studies, the researchers found that mice without FUT8 — which are less likely to develop ulcerative colitis — had a thinner mucous layer than those with more FUT8.
“This study shows that changes in the quantity and quality of this mucus are a major cause of the initial inflammation observed in ulcerative colitis. The researchers found that patients with UC have increased levels of FUT8 in the colon. This fits with the finding that mice deficient in the FUT8 gene are protected from UC.”
— Dr. Harry Thomas
Although thicker, the mucous layer in mice with more FUT8 was less compact and more permeable, so allowed bacteria to reach the epithelial cells of the colon. The mucus was also stickier, so bacteria became trapped within it, giving them more time to invade nearby cells.
Dr. Gerard Cantero-Recasens, junior principal investigator at the Vall d’Hebron Research Institute (VHIR), and one of the co-authors of the study, further explained:
“In contrast, when FUT8 is depleted, epithelial cells secrete mucins that form a more compact mucus. This makes the mucous layer less permeable, and easily washed away. Since cells continuously secrete more mucins, bacteria that are trapped within mucus are constantly removed. We believe that [fewer] bacteria means less contact with the epithelium, which in turn prevents or reduces inflammation.”
How the microbiome gets affected
In healthy people, the mucus forms two layers, an inner layer attached to the wall of the colon that is impermeable to microbes and bacteria, and an outer layer that is colonized by beneficial and harmful bacteria. This outer layer is constantly washed away and replaced.
High levels of FUT8 alter the mucins so that the mucous layer is more permeable but resistant to washing away.
The researchers suggest that these changes in the composition and viscosity of the mucous layer cause the inflammation seen at the start of UC.
The authors also suggest that changes in the mucous layer may affect the microbiome — the population of beneficial microbes that inhabit the intestine. This may, in turn, cause an immune response.
They suggest that further study should investigate the gut microbiome of people with UC and healthy people, to see whether there are differences.
How UC could be diagnosed early
Feces contains mucus from the colon, so the researchers propose that stool samples could be used for early diagnosis of UC.
In people with UC, FUT8 alters the ratio of different mucins, so measuring levels of fucosylation, or of certain mucins in the stool samples, could detect the condition and measure its progress.
Prof. Vivek Malhotra, the senior author of the study and ICREA Research Professor at the Centre for Genomic Regulation (CRG), told MNT “[l]ess mucus in the stools would also indicate more fucosylation,” so lower mucus content might indicate UC.
He also suggested that stool analysis might be useful as a part of treatment, saying that it “could be also used as a starting point to provide prognostic biomarkers to anticipate ulcerative colitis progression or flare-ups.”
Dr. Thomas agreed, but stressed the need for further research: “The concept of a stool test that is specific for ulcerative colitis raises exciting possibilities for both initial diagnosis of the condition as well as subsequent monitoring during treatment; however, this would require further research and validation in patients.”
“Even more intriguing is the possibility of using such a test to predict whether at-risk individuals (e.g. family members of affected patients) might develop ulcerative colitis in the future; again, this would require much more research,” he added.
Source: Read Full Article