First ever trial of fecal microbiota transplantation in humans with ulcerative colitis successful.
There is currently great interest in treating ulcerative colitis with fecal microbiota transplantation (FMT), which involves transplanting gut fecal bacteria from healthy people into patients with ulcerative colitis. Now, two new studies, one animal and the other human, by researchers from McMaster University show that transplantation of fecal matter may be a useful tool in the fight against ulcerative colitis.
Previous studies show that ulcerative colitis is a chronic, debilitating inflammatory bowel condition characterized by symptoms including bloody stools, diarrhea, abdominal pain, weight loss and malnutrition. It results from the development of abnormal immune responses to the normal bacteria in the digestive tract. It is difficult to treat and standard therapy doesn’t always work.
The first new study from the team uses an animal model and is published in the journal Inflammatory Bowel Diseases. The data findings showed that ulcerative colitis can be controlled by the type of bacteria that inhabits the gut. The team state that the animal research provides insight that selected bacterial groups, involved in gut health, are important for protecting the colon against injury and inflammation.
The second new study from the team is a clinical human trial published in the journal Gastroenterology. The team explored the safety and efficacy of FMT by conducting a placebo-controlled, randomized trial. The results showed that FMT induces remission in a significantly greater percentage of patients with active UC than placebo.
The researchers state that to their knowledge the current study in patients with ulcerative colitis is the first randomized trial of fecal microbiota transplantation in adults with ulcerative colitis. On top of this the data findings also show that this therapy may work. They go on to add that the effect of fecal transplant seems to be dependent on the sort of bacteria that is in the donor stool, which fits with the observations of the animal study.
In the animal study, mice were given gut bacteria from patients with severe ulcerative colitis and the effects were compared to those produced in mice that were given bacteria from a healthy person. The results identified a reduced amount of the bacterial families that are important for gut health in the feces of patients with severe colitis.
The results showed that when mice were given these bacteria and then exposed to a toxin that causes gut injury, the resulting inflammation was higher in the mice with ulcerative colitis bacteria than in mice with bacteria from the healthy person, in whom the beneficial bacterial groups were abundant. The data findings also showed that the same protective effect could be achieved using the fecal material from the healthy person as with specific groups of bacteria that were isolated from the ‘healthy’ fecal matter. The team ssuggest that specific combinations of beneficial bacteria extracted from healthy people could be tested in future clinical fecal transplantation studies, and could potentially replace fecal matter.
The team state that the implications of the animal study relate to the selection of healthy donors for fecal transplantation. The researchers note that in addition to screening for infections and disease, donors that harbour an abundance of the beneficial bacterial groups identified in the animal study could be selected to increase the chances of success of transplantation.
This was validated in the human study which recruited 75 patients with a flare up of their ulcerative colitis. The patients were randomized to fecal transplant therapy given as an enema derived from stool donated by an anonymous healthy donor once per week for six weeks, or a placebo consisting of a water enema. The results showed that 24 per cent were in remission in the fecal transplant group compared to five per cent in the placebo group.
The researchers note that out of two main healthy donors, donor A and donor B, one of which was the healthy donor from the animal study, the benefit seemed to be mostly related to those that received stool from donor B. The effect was also greater in those that had recently been diagnosed with ulcerative colitis.
The team surmise that many questions remain, however their studies provide interesting data suggesting that altering the gut microbial flora may be promising for treating ulcerative colitis. They conclude that their data also suggests more research is needed using the FMT approach.