Flushing out new cures for intestinal disease

People with good digestion

You can’t blame Patient #1 for not wanting to share his name; he’d rather not be known as the guy who swallowed poop in the name of science.

But he does want you to know he is willing to go to extremes to help find a cure for Crohn’s disease, an autoimmune disorder that causes severe abdominal symptoms and robs his body of nutrients.

It’s not as crazy as it sounds. Fecal microbiota transplantation (that’s right – fecal, as in feces, as in poop) is a tried-and-true treatment for recurrent bouts of Clostridium difficile infection (or C. diff), a dangerous intestinal bacteria.

It works by repopulating the intestinal tract with “good” bacteria, which are often wiped out by the antibiotics used as the first line of defense against C. diff.

What’s not known is whether fecal transplant can also help patients with inflammatory bowel disease, like Crohn’s disease and ulcerative colitis.

A team at Seattle Children’s – led by gastroenterologist David Suskind, MD – is carrying out a clinical trial to answer that question.

First center to test fecal transplant effectiveness in pediatric patients

Children’s was the first research center in the nation to receive federal approval to test the effectiveness of fecal transplants in pediatric patients with inflammatory bowel disease, and it is the only center studying the treatment in children with Crohn’s disease.

More than a coincidence?

As is often the case, this clinical trial was inspired by a patient’s clinical experience.

About a year ago, the Gastroenterology team used fecal transplant to treat a stubborn C. diff infection in a patient who also had ulcerative colitis. “The patient’s C. diff infection improved,” says Suskind. “Even more significantly, the patient’s inflammatory markers went down, a sign that the ulcerative colitis had also improved.”

Was it just a coincidence? To find out, Suskind needed to test the treatment in other patients.

Within nine months, he had approval from the Institutional Review Board at Seattle Children’s Research Institute; permission from the U.S. Food and Drug Administration to proceed with a clinical trial; and funding from Seattle Children’s Academic Enrichment Fund.

The goal is to study 20 patients, ages 12 to 21, who have mild to moderate disease.

Patient #1 fit the criteria

The 19-year-old college student has been living with Crohn’s disease – and coming to Children’s for care – since his sophomore year of high school. When it flares up, the illness lays him low with pain and diarrhea.

“Crohn’s is a big part of my life,” he says. “I had to stop a lot of physical activities in high school, like sports. And I didn’t do as well academically my junior and senior years because stress makes my symptoms worse.” The disease typically sidelines him from school for a week or two each year.

Medications to control the symptoms work at first, he says, “but eventually the effectiveness wears off and I have to switch.”

He was on his third medication when Children’s got the go-ahead for the fecal transplant trial. He was the first patient to enroll.

“This offered something besides regular medication,” he says. “Even though it might not benefit me, I didn’t see how it could hurt. And I like the idea of helping move the science forward.”

He was undaunted by the “ick” factor. When you’ve lived with Crohn’s disease long enough, he reasons, you get used to dealing with poop.

No taste, no smell

Unlike an organ transplant that requires surgery, fecal transplant is a pretty simple procedure, explains Suskind:

• Stool is donated, usually by a family member, and is screened for infection.
• The patient prepares for the procedure by taking antibiotics and a laxative.
• A solution of donor stool mixed with saline is administered through a tube running from the patient’s nose to their stomach (this takes about three minutes).
• A half hour later, the patient goes home.

“Dr. Suskind distracted me while they put the stuff in the tube, and I didn’t even notice it going in,” says Patient #1. “There was no smell and no taste, and it was over pretty quickly.”

All in all, it’s simple and low-risk, says Suskind.

“Fecal transplant has been used to treat C. diff in patients from 2 to 90 years old with no overt side effects,” says Suskind. “While there’s a hypothetical risk of transferring an infection, our screening procedures vastly reduce that risk.”

Patients come back for check-ups and lab work two, six and 12 weeks after the procedure.

Patient #1 felt better after the transplant, and blood tests showed a dramatic drop in his inflammatory markers at his two-week and six-week follow-up visits.

These preliminary results give Suskind and his team reason to be cautiously optimistic.

“Trillions upon trillions” of bacteria

While the researchers try to figure out whether fecal transplant helps patients with inflammatory bowel disease, they’re also trying to learn why these diseases occur in the first place.

“We have more bacteria in our bowels than we have cells in our bodies – trillions upon trillions of them,” explains Suskind. “Our best guess is that in individuals with inflammatory bowel disease, bacteria that are not healthy for the gastrointestinal tract take hold, triggering an immune system response that results in inflammation of the lining of the intestine.”

That inflammation can lead to debilitating abdominal pain, diarrhea, growth failure and nutritional deficiencies.

But why, exactly, does this autoimmune response occur in some people and not others? And, precisely which bacteria are involved?

“As yet, nobody knows for sure,” says Suskind. But that is sure to change.

“This is a golden age of research for inflammatory bowel disease,” he says. “A lot of research coming out now is helping us better understand the tremendous diversity of bacteria that live in our bowels.”

Children’s fecal transplant study will be an important addition to the body of evidence.

“We don’t know yet if this works – and if it does, we don’t know whether it will completely transform the intestinal biome in the long run,” says Suskind. “That’s why our patients are so important. They are the key to answering the questions.”

Note: The U.S. Food and Drug Administration recently told NBC News and other outlets that they now require doctors and clinics that perform fecal transplants to apply for investigational new drug applications, known as INDs, in order to continue their work. Dr. Suskind told On the Pulse that Children’s has an IND for its study.

To arrange an interview with Dr. Suskind, contact the Seattle Children’s public relations team at 206-987-4500 or via [email protected].

Update: Seattle Children’s is no longer doing this trial. The results are being analyzed and will be reported on in the future.