Jonathan Tybur’s swimming career rebounded after treatment. Today, he competes on the Texas A&M University swim team.
By Rosanne Moore
The trillions of bacteria, viruses and fungi that call our bodies home may represent a new frontier in the treatment of inflammatory bowel disease. Texas Children’s researchers are exploring fecal bacteriotherapy, which has the potential to dramatically improve the quality of life for children with ulcerative colitis.
THE DEBILITATING FOE
It happens again. Another flare-up. The symptoms are humiliating: crippling abdominal pain, bloody stools and mortifying dashes to the bathroom. This isn’t a 24-hour stomach bug. Instead, it’s the unpleasant reality for patients with ulcerative colitis (UC).
Casey Cook, 17, and Jonathan Tybur, 19, know this reality all too well. Four years ago, they were diagnosed with this devastating bowel condition that inflames the inner lining of the large intestine or colon.
This two-word diagnosis — ulcerative colitis — turned their lives upside down. While most teens their age enjoy the simple pleasures in life — swimming, traveling and hanging out with friends — these outings can be filled with anxiety due to the disease’s unpredictable nature.
“You never know when an attack will happen,” Tybur said. “It usually strikes without warning.”
Ulcerative colitis progresses slowly, and the symptoms may not be easily detected until the inflammation is severe. Most patients experience rapid weight loss, swollen joints, tainted stool, sharp abdominal pain, and violent and frequent episodes of diarrhea.
“When I was diagnosed, I remember feeling this stabbing pain in my stomach that made me double over,” Cook said. “By the time I went to the hospital, my entire colon was inflamed with ulcers.”
Patients with UC have medical and surgical treatment options. The medical treatments include anti-inflammatory steroids and other powerful immunosuppressant/immune-modulator drugs. The surgical option is essentially the removal of the colon. The disease is more aggressive in children than adults, with up to 40 percent of children requiring colon removal within 10 years of diagnosis, according to studies in the past decade.
Cook’s and Tybur’s treatment regime included a powerful combination of steroids and immunosuppressant medications. While it controlled the symptoms, it produced side effects, and some of the medications were known to increase the potential risk for certain types of cancers.
“I would get very irritable, very bipolar, and I had problems with infection because my immune system was altered,” recalled Tybur.
The treatments drained Cook’s energy.
“I felt tired all the time, extremely hungry and depressed,” he said.
FINDING A BALANCE
Texas Children’s is among very few hospitals across the nation exploring fecal bacteriotherapy, or fecal microbiota transplantation (FMT), a nonconventional treatment that transplants stool from healthy donors into the colon of UC patients in an attempt to restore a healthy, diverse bacterial population in the gut.
“We believe it is beneficial to have a more diverse, complex community of bacteria and microorganisms in our intestinal tract because it is a denominator of good health,” said Richard Kellermayer, MD, a pediatric gastroenterologist and clinical initiator of the investigative Intestinal Microbiome Transplantation program at Texas Children’s.
While the cause of UC is unknown, researchers believe that an imbalance of the bacterial community in the colon may cause the immune system to overreact, triggering the chronic intestinal inflammation. In theory, restoring the colonies of helpful bacteria through FMT may induce a healthier microbial community that could reset the patient’s immune system and stop the chronic inflammation, resulting in long-term remission.
Transplanting stool from one person to another may sound repulsive, but surprisingly a majority of the matter in stool — roughly 60 percent — come from live and dead bacteria. While bacteria can make us sick, they also constitute a large part of who we are. Stool transfer or transplantation from a healthy individual can in fact treat intestinal infections by disease-causing bacteria, as in the case of Clostridium difficile infections (colitis), where conventional antibiotic treatments have failed.
The trillions of cells in the human microbiome roughly outnumber human cells 10 to 1. While these diverse microbes populate the inside and outside of our bodily surfaces, they perform vital functions, including aiding our normal development, digestion, hormone regulation and immune system responses.
“Patients who have used fecal bacteriotherapy to treat antibiotic-induced Clostridium difficile intestinal infections have seen up to a 90–95 percent success rate,” Kellermayer said. “We are exploring this therapeutic treatment alternative for UC patients so they don’t have to endure the severe side effects of immunotherapy.”
PUTTING GUT MICROBES TO THE TEST
Kellermayer is the lead investigator of an ongoing, Phase I study at Texas Children’s that examines the safety and tolerance of fecal bacteriotherapy in 10 immunotherapy-dependent patients with UC.
Unlike most clinical trials that have used a maximum of five fecal transplants, this study uses 37 fecal enema treatments over the course of one year. The lab-prepared stool samples are supplied by healthy, anonymous donors who have undergone a meticulous screening process to ensure patients are not exposed to unreasonable risks.
Since human stool is considered a drug and a biologic when used to treat disease, an Investigational New Drug (IND) approval was obtained from the U.S. Food and Drug Administration (FDA).
“The Texas Children’s Hospital Research Resources Office has provided extraordinary help in obtaining the IND approval,” Kellermayer said.
This clinical study is being conducted in collaboration with Texas Children’s Pediatric Gastroenterology Division, Texas Children’s Microbiome Center, and the Department of Molecular and Human Genetics at Baylor College of Medicine.
“The Microbiome Center led by Dr. James Versalovic is an implemental part of this treatment trial,” Kellermayer said. “They are helping us tremendously with the screening, collection, filtration and storage of the donor stool for transplantation.”
Six UC patients have enrolled in the fecal microbial transplant study, including Tybur and Cook, who have seen a dramatic improvement in their quality of life. Four patients with moderate to severe UC at the time of enrollment were withdrawn from the study for lack of response. This is why the trial is currently under modification and will be geared toward patients with mild UC disease activity or who are in clinical remission, but who would like to trade their immunotherapy with significant long-term side effects for a potentially less harmful treatment option, which may even be curative in some cases.
Tybur is the only patient who completed 28 fecal enema treatments within three months before the FDA required IND approval. After completing the trial, Tybur relies on decreased doses of immunosuppressants to keep his symptoms at bay.
“The treatments definitely improved my life and changed the pattern of my disease,” Tybur said. “I used to have all these symptoms that would come out of nowhere. Now, it is more manageable.”
Cook re-enrolled in the study — the clinical trial was stopped temporarily after the FDA changed its rules requiring IND approval — and is receiving fecal transplants once a month. He started off with daily treatments for two weeks, then three times a week for two weeks, once a week for eight weeks, and now once a month.
“I have very minimal recurrence of colitis symptoms,” Cook said. “I can do things that I wasn’t able to do, like jog, exercise and socialize with my friends without having to constantly worry about stuff.”
While the trial’s preliminary results are promising, Kellermayer said, “Learning the microbial composition in a healthy donor’s fecal microbiome, and the changes in the microbiome of the patients during the treatments, could lead to new therapies that target the disease’s underlying cause rather than just suppress its symptoms.”
Despite the volatile nature of UC, there’s one thing this disease did not strip away: Cook’s and Tybur’s freedom to pursue their passions.
As a high school athlete, Tybur was a competitive breaststroke swimmer and still is today. Before his diagnosis, he was competing at national level swim meets and was one of the top breaststrokers in the nation in his age group of 13- and 14-year-olds.
“When he was diagnosed with UC, his swimming career tanked,” his mom Marcy Tybur said. “After participating in Kellermayer’s clinical trial, Jonathan’s swimming career miraculously rebounded.”
“When I was going through the treatments, I went from not even placing in the top eight at districts to being second in the state and winning a state medal in high school,” Tybur said.
As a college sophomore, Tybur hopes to add to his medal collection as he competes on the Texas A&M University swim team. He has now qualified for the 2016 Olympic trials in 100m and 200m breaststroke. As for Cook, he is refining his culinary skills in the kitchen.
“I love to cook,” said Cook. “I’ve recently come up with my own flavored rum cakes, which I’ve been selling like crazy.”
To add to this milestone, Cook has been accepted into the coveted culinary program at his high school.
“It is really exciting to see him chase his dreams,” his mom Adrien Cook said. “I can see the life in his face again. The treatments have truly been a major life changer in our house.”
Continue to Too Deeply Attached