Scientists have linked a missing gut microbe to ulcerative colitis, opening the door to a possible new treatment.
A team of scientists from Stanford University School of Medicine in California has identified a gut microbe that is deficient in people with ulcerative colitis. This finding may be key to why some individuals develop ulcerative colitis.
The research appears in the journal
The scientists hope that by replacing the function of this missing microbe, it may be possible to develop new and more effective treatments for ulcerative colitis.
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The symptoms of ulcerative colitis can range from mild to severe, and there is currently no cure. Instead, treatments focus on keeping the disease in remission for as long as possible.
Treatment usually begins with medications, but if these do not work, surgery may be necessary.
According to the Crohn’s and Colitis Foundation of America, 23–45% of people with ulcerative colitis will eventually need to have surgery.
Surgery involves the complete removal of a person’s colon and rectum. The surgeon will then create either a stoma, which acts as an external pouch to collect intestinal contents, or an ileoanal reservoir, which is a J-shaped pouch at the end of the small intestine that does the same job.
Until now, scientists have not been sure why ulcerative colitis affects some people and not others. The new research from the team at Stanford suggests that a key reason may be the lack of particular gut microbes.
When patients undergo a colectomy or surgical removal of the colon, doctors often attach the small intestine to the anus to reconnect the digestive tract. They then replace the rectum or end of the colon with a pouch made from the small intestine, called a J pouch.
The J pouch functions as a “pseudo-rectum,” allowing patients to store stool prior to defecation. In patients with inflammatory bowel disease, it has been shown that the J pouch can often become inflamed over time — a condition called pouchitis.
Two common reasons to obtain a colectomy and J pouch include ulcerative colitis and a genetic condition called familial adenomatous polyposis (FAP). Ulcerative colitis is an inflammatory bowel disease, while FAP is not. Research has found that patients with ulcerative colitis are more likely to develop pouchitis than those in patients with noninflammatory disease such as FAP.
The researchers wanted to work out why this was the case. To do so, they compared two groups of participants, one with FAP and the other with ulcerative colitis, looking for any significant differences between them.
They found that a key difference was the presence of a type of secondary bile acid in the intestines, which was in far greater quantities in those with FAP than in those with ulcerative colitis. One possible reason for this deficiency could be the lack of a specific gut bacteria responsible for the production of these bile acids.
The scientists were able to identify a specific bacterial family called Ruminococcaceae that was underrepresented in those with ulcerative colitis pouches.
Ruminococcaceae bacteria are the main type of microbe that converts primary bile acids into secondary bile acids. These acids appear to serve an anti-inflammatory effect in patients with pouchitis, although the mechanism by which this occurs is unclear.
As Dr. Aida Habtezion, an associate professor and senior author of the study, notes: “All healthy people have Ruminococcaceae in their intestines. But in the [ulcerative colitis] pouch patients, members of this family were significantly depleted.”
Helping to confirm their findings, the investigators found that stool samples from the participants with FAP and ulcerative colitis pouches turned primary bile acids into secondary bile acids in significantly greater quantities than samples from those with ulcerative colitis.
The team then gave secondary bile acid supplements to mice who had induced colitis to replace any missing secondary bile acids. This reduced inflammation as well as the normal symptoms of colitis in mice.
“This study helps us to better understand the disease,” says Habtezion.
“We hope it also leads to our being able to treat it with a naturally produced metabolite that’s already present in high amounts in a healthy gut.”
— Dr. Aida Habtezion
To get to this point, the team is now conducting a clinical trial to discover whether a secondary bile acid supplement can help people with refractory pouchitis. If these studies are successful, we may one day be able to apply these findings to additional studies on treating ulcerative colitis itself.