The finding could help develop new therapies, especially for treating pouchitis, colitis-like inflammation that frequently occurs in the roughly 25 percent of UC patients who eventually undergo J-pouch surgery. Right now, antibiotics are the only known way to treat pouchitis, but antibiotics don’t just target the bad bacteria. Frequent use of antibiotics decimates beneficial gut bacteria, too. In a study published in February 2020 in the journal Cell Host & Microbe, researchers compared stool samples from people with UC who underwent ileal pouch-anal anastomosis (IPAA) surgery, or J-pouch surgery, with people who had the same surgery for an unrelated condition called familial adenomatous polyposis (FAP). (Unlike colitis patients, FAP patients who undergo colon removal rarely develop pouchitis.) Compared with patients with FAP, the microbial diversity in UC pouch patients was largely diminished, especially a single family of bacteria called Ruminococcaceae. The researchers also discovered that this family of bacteria is a key player in anti-inflammatory processes in the gut. “All healthy people have Ruminococcaceae in their intestines,” says Aida Habtezion, MD, associate professor of gastroenterology and hepatology at Stanford University in California, and senior author of the study. “Now that we know they are beneficial, we can study how to make them grow better.” According to Alexander Khoruts, MD, director of the University of Minnesota microbiota therapeutics program in Minneapolis, who was not involved in the study, Ruminococcaceae are one of the few types of bacteria involved in converting bile acids, which are produced in the liver and are needed to properly digest fat and fiber. Bile acids eventually funnel into the colon, where bacteria like Ruminococcaceae turn them into secondary bile acids with anti-inflammatory properties. Without the proper bacteria, bile acids can’t enter their second phase of life, in which they keep inflammation at bay. Researchers also analyzed bile acid profiles for patients with UC versus FAP and found that UC patients had nearly nonexistent amounts of the two most common secondary bile acids, lithocholic acid (LCA) and deoxycholic acid (DCA), which are known influencers of the inflammatory response.
Adding Tools to the Toolbox
In a second part of the study, Dr. Habtezion and her team inoculated mice with the two bile acids in which UC pouch patients were deficient. They wanted to expand the study to look at how these microbes might apply to the larger inflammatory bowel disease (IBD) population. In the experiment, the added bile acids reduced inflammation in mice, which represented UC patients who did not undergo surgery. Although studies conducted on mouse models are rarely accurate portrayals of how medicines or therapies will function in the human body, the discovery does open the door for further research that could help develop new therapies for people with IBD. “The treatments for IBD that we have are all about depressing the immune system since inflammatory bowel disease is thought to result from instrumental immune responses that change the microbes that reside in the gut,” says Dr. Khoruts, noting that this change causes the immune system to attack its own body as it would a dangerous intruder. While the new study gives researchers a lot to expand upon, Khoruts is careful to consider the differences between UC pouch patients, who typically consume more gut microbe–killing antibiotics than nonpouch UC patients. Despite causing similar symptoms, a colitis flare-up biologically is not the same thing as pouchitis, and antibiotics are not used to treat UC, as they are pouchitis. “Pouchitis is clinically important to that population, but it is a bit of a stretch to say what applies to them also applies to general UC patients,” he says. “They are different diseases.” Still, this new information related to the microbes affected by UC could shape novel therapies that focus on the root of the issue rather than the symptoms, he says. It could also cut down on antibiotic use in UC pouch patients. According to Habtezion, future research should explore whether or not particular foods stimulate the growth of these bacteria. If we know which nutrients the bacteria prefer to feast on, dietary therapies could be an effective IBD treatment option in the future, she says. Khoruts says another possibility could be to create synthetic versions of bile acids or bacteria that minimize side effects and maximize anti-inflammatory benefits. “We have these designations, UC or Crohn’s disease, but we have the same treatment for everybody. The long term goal is that treatment would be more personalized. We would incorporate all the tools we have and we wouldn’t just target the immune system, but the multiple factors that contribute to inflammation,” says Khoruts.
