Ulcerative colitis: bacteria findings raise hopes for new treatment

Hopes of developing a new treatment for ulcerative colitis have been raised by research suggesting the condition may be linked to low levels of certain bacteria in the gut.

Ulcerative colitis is a long-term condition in which the colon becomes inflamed. According to the NHS, it is thought to be an autoimmune disease and affects one in every 420 people in the UK. Sufferers need to empty their bowels frequently, develop ulcers in their colon and have recurring bouts of diarrhoea with blood and pus in the faeces.

While a number of medicines can help manage the condition, ulcerative colitis can only be cured by removing the colon. However, about half of those who have this surgery go on to have inflammation in the area of the small intestine that is reconstructed into a pouch to serve as a rectum. Such inflammation is treated with antibiotics.

Now researchers say patients who have had this surgery for ulcerative colitis have lower levels of certain acids in their faeces, and fewer of the bacteria that produce them, than those who have had the surgery for other reasons.

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The team say the results shed light on why the latter have a far lower risk of inflammation in their pouch. They say it also offers insights into ulcerative colitis itself, with experiments in mice suggesting inflammatory bowel diseases could be treated by introducing these “missing” acids into the colon.

Dr Aida Habtezion, a co-author of the study from Stanford University, told the Guardian the findings suggest a new approach to treating ulcerative colitis could be developed, based on introducing microbes or the substances they produce.

Many patients find current treatments do not work or have side-effects. “I think it brings another mechanism, a natural way, in which we can reconstitute and hopefully treat our patients,” Habtezion said.

Writing in the journal Cell Host & Microbe, the team report how they studied two groups of patients who had had their colons removed and pouches created. For one group, of 17 patients, this surgery was to treat ulcerative colitis whereas for the other group, of seven patients, it was because of a different condition that does not involve inflammation.

Certain bacteria in the gut are known to convert bile acids, produced by the liver, into other substances, called secondary bile acids – these substances have recently been suggested to have an anti-inflammatory role.

The team analysed faeces from patients in each group, finding that patients treated for ulcerative colitis had far lower levels of certain secondary bile acids than the other group. Their faeces contained far less evidence of bacterial genes necessary for the production of these substances.They also had less diverse bacteria in their faeces that the other group, and more specifically, far lower levels of ruminococcaceae. Such bacteria are among those able to convert bile acids to secondary bile acids.

Experiments in mice with three different conditions comparable to ulcerative colitis or Crohn’s disease – another disease where parts of the digestive system becomes inflamed – offered further insights. They found that introducing these secondary bile acids reduced markers of the disease, such as inflammation.

Habtezion said the findings chime with other research that has suggested patients with inflammatory bowel disease have lower levels of secondary bile acids. However, she said it was still unclear if the shift in bacteria and depletion of secondary bile acids were a cause or an effect of such conditions.

The team is carrying out a clinical study to explore whether introducing secondary bile acids may help to treat patients who have had surgery for ulcerative colitis but who develop inflammation in their pouches.

Dr Gwo-tzer Ho, a consultant gastroenterologist and expert on ulcerative colitis at the University of Edinburgh, welcomed the study and the ongoing clinical trial. He said that, if successful, the approach could be particularly helpful for those who also had a condition called primary sclerosing cholangitis – a disease of the bile ducts.

But he said it was important to investigate further whether a dearth of similar bacteria, and the secondary bile acids they produce, was seen in the colons of those with ulcerative colitis who had not had surgery.

“This [study] provides further clues [about] the roles of bacteria and bile acids, potentially in the development of ulcerative colitis,” he said.