June/July 2016

Microbiome Study of Inflammatory Bowel Disease Will Give the Gut a Holiday

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Lindsey Albenberg, DO, wants to give her patients’ guts a vacation.

Dr. Albenberg, a pediatric gastroenterologist at The Children’s Hospital of Philadelphia, is launching a new study of Crohn’s disease that gives the digestive tract a “holiday” by temporarily wiping out the bacteria and fungi that populate it. A growing weight of evidence suggests that this population of microbes, known as the gut microbiome, plays an important role in triggering the body’s excessive and painful immune response in this and other forms of inflammatory bowel disease (IBD).

“It’s a very bacterially mediated disease,” said Dr. Albenberg, who is also an assistant professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania. The most common treatments for IBD involve antibiotics and drugs that suppress inflammation and the immune system, but only some patients respond to these treatments. Many patients continue to have painful and unpleasant symptoms, ranging from abdominal pain to diarrhea and blood in the stool.

A clue to this new approach comes from the fact that some patients experience temporary relief after undergoing ileostomy, a surgical procedure that diverts digestive products before they reach the colon. The process starves bacteria and other microbes, leading Dr. Albenberg and her collaborators to hypothesize that dramatically reducing the colon’s population of microbes could offer some patients a similar benefit without the undesirable procedure.

She was recently awarded a pilot grant from the Broad Program at the Crohn’s and Colitis Foundation of America to begin this new HOLIDAY study. The study will enroll 20 adults at Penn and 20 children at CHOP, all of whom have Crohn’s disease that does not respond to the best available medications. Participants will empty their digestive tracts’ contents in a process similar to preparing for a colonoscopy, then take a combination of antimicrobial drugs intended to drastically reduce the population of microbes in the gut.

Dr. Albenberg and her colleagues will monitor patients’ clinical symptoms during treatment and after for six months using a validated disease activity score; measures of inflammation including biomarker proteins in blood and feces; and microbiome measures of the bacterial and fungal load, bacterial and fungal composition, and metabolites produced by the gut microbes. They hope to correlate changes in both bacterial and fungal load and bacterial and fungal composition with the outcome measures. The focus on fungi in this study is a rare but emerging focus among microbiome studies.

“We published a paper about a year ago that showed differences in the fungal microbiota in children with IBD at CHOP, as compared to healthy controls,” Dr. Albenberg said. “There were significant differences in the composition of gut fungi. So this is now a question: Should we be treating IBD patients with antifungal medications?”

HOLIDAY study participants will be randomized so that half take an antifungal drug in addition to the multiple antibiotic drugs taken by all study participants.

Dr. Albenberg noted that this small study is exploratory but could provide a wealth of information about the role of the microbiome in Crohn’s disease, as well as about the process of repopulating microbes after treatment. Because the disease is so heterogeneous, she does not expect all patients to respond to this treatment, but she believes that some might.

“I think ultimately this could be a stepping stone to many other projects,” she said. “Even if it doesn’t work for everyone, we’ll learn a lot about the microbiome in people with IBD who are refractory to the best medications that we have out there. If it works, then I think that it opens up the door for novel treatment methods with antimicrobial medications.”

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