A New Less-Than-Expected Gastrointestinal Treatment
By Maria Dolan
April 6, 2015
A revolutionary new gastrointestinal treatment takes guts
In 2009, a Seattle-area property manager, Michael (who asked that we not use his last name), developed a minor case of diverticulitis, a not uncommon digestive disease. His doctor prescribed strong antibiotics, but he didn’t get better. Instead, Michael came down with another gut infection, caused by a type of bacteria called Clostridium difficile, or C. diff. It’s a disease that can, in the worst cases, lead to organ failure and death. Over four months, Michael withered from 165 pounds to 125 pounds, and his bank account shrank, too—his medical treatments cost thousands of dollars, including an antibiotic that cost about $1,000 for a two-week supply. But the drugs relieved his symptoms. Without them, the agony returned. Michael toughed out his day job on a liquid diet, making dozens of trips to the bathroom because of diarrhea, and doubling over in pain from abdominal cramps and back spasms. Every weekend, he’d pack up and check himself into a nearby hospital to hook up to an IV drip. “I was at the point where I could hardly stand,” he says. “It just wouldn’t let go.”
Finally a friend, also a doctor, made a suggestion. Maybe Michael should consider getting a stool transplant. The friend had heard about a gastroenterologist at Harborview Medical Center who was using this bizarre-sounding procedure (officially, fecal microbiota transplantation) to cure C. diff. It involved taking stool from a healthy donor—often a relative—and transferring it to the colon of a C. diff sufferer via colonoscopy.
Soon after, Michael found himself at Harborview Medical Center, meeting his new doctor, Christina Surawicz. A distinguished physician in her field, she has been a gastroenterologist at the hospital since 1981 and is a professor of medicine at the University of Washington School of Medicine. Like a regular colonoscopy, she told him, a stool transplant would take about an hour, and included sedation, plus a two-hour recovery. She also told him the procedure has a 90 percent success rate after just one treatment, and might be the only thing that would cure him; after three courses of antibiotics for C. diff, a patient is less likely to kick the bacteria with medication alone.
After his initial meeting with the doctor, Michael made his decision overnight. “I just had to get through the initial shock of what the procedure entailed,” he says. He found a relative from out of town who was willing to fly in and donate. Michael felt better within a day of his transplant, and spent another year recovering his strength. “It was a terrible, terrible, terrible time,” he says of his months of illness. By comparison, the stool transplant was easy.
The fecal transplant preparation area in a special utility room at Harborview Medical Center; Photo Credit: Easton Richmond
Donors—and their stool—are extensively screened. Blood tests and a questionnaire scan for communicable diseases, including hepatitis A, B and C, HIV and syphilis; immune disorders; and diarrheal disorders such as irritable bowel disease and celiac disease. Stool is tested for a long list of pathogens, including C. diff, enteric pathogens such as E. coli and salmonella, giardia, parasites, rotavirus and cryptosporidium. The screens also look for cancer, diabetes, obesity, chronic pain syndromes and neurologic disorders, which may potentially have links to gut bacteria. Harborview asks patients to identify a potential donor, although doctors have sometimes found a staff member or donor for another transplant who is willing to help. Harborview recently began purchasing stool—screened and then frozen—from the country’s first stool bank, Open Biome, in Massachusetts. It’s $250 per preparation, plus shipping and handling.
Fecal transplantation has a very long history. According to a New Yorker article on the topic last year, a fourth-century Chinese handbook holds the first known account of the practice, which was used as a cure for diarrhea. Surawicz was one of the first doctors in Seattle to adopt the modern form of the procedure. She had been studying probiotic treatment for C. diff, which was somewhat but not uniformly effective, and tried fecal transplant in last-resort cases. After a gastroenterologist she respected published successful results in 2000, and as evidence mounted that fecal transplantation was effective and low-risk, Surawicz began recommending the treatment in 2004 to patients who had had three rounds of antibiotics for C. diff without being cured.
The U.S. Food and Drug Administration has classified stool transplants as experimental drug treatment, and for a few months in 2013 was requiring an Investigational New Drug Application to use the treatment, but has since relaxed those rules. Surawicz says transplants have become more common both because of their phenomenal success rate, and also because hypervirulent strains of C. diff have emerged in the last decade—probably in response to the use of certain antibiotics—leading to a huge spike in cases, and deaths. According to the Centers for Disease Control and Prevention (CDC), the estimated number of deaths attributed to the illness increased from 3,000 deaths per year during 1999–2000 to 14,000 during 2006–2007. While the primary risk factor associated with C. diff is antibiotic use, other factors generally include older age and time spent in a hospital or long-term care facility; yet, in recent years, the population contracting the illness has broadened. “We’re seeing more reports of C. diff in outpatients, healthy people, people who haven’t even had antibiotics, young people and pregnant women,” says Surawicz. The CDC says the bacteria is often transmitted between patients by the hands of caregivers—the spores are resistant to common hospital disinfectants and deterred only with special cleansers and the use of gloves—but, Surawicz notes, waving a hand at her office carpet, “It’s all over the place. If we cultured the floor, we’d probably find it here.”
Clostridium difficile (yellow cells) cause an intestinal infection that can be treated with a fecal transplant; Photo Credit: Science Photo Library
No one is entirely sure how transplants evict bad bacteria, but it’s a good guess that microbes beneficial to the human gut are responsible. The transplanted stool reintroduces bacterial strains that are beneficial to the gut and that decrease with antibiotic use. This microbial diversity appears to keep C. diff in check. The treatment spotlights an astonishing fact researchers didn’t understand until relatively recently: We are more microbe than human, containing multitudes of microbes—about a hundred trillion of bacteria, viruses and fungi, and thousands of different types, everywhere from our mouths to our guts to our armpits. Collectively, this is referred to as our microbiome, and the digestive tract is its New York City, teeming with tens of trillions of microbes. These collectively act like an organ, and one we can’t live without.
“We’re actually walking flasks of bacteria,” says Dr. David Suskind, an expert in intestinal diseases at Seattle Children’s Hospital and an associate professor of pediatrics at the University of Washington School of Medicine, who is studying the use of stool transplants, administered via a nasogastric tube (through the nose and throat to the stomach), to fight Crohn’s disease, an inflammatory bowel disease, in children. In his first trial, the majority of Crohn’s patients experienced clinical improvement and remission following transplant. These microbes, he says, play an extremely important role in health by making proteins and other molecules, helping to break down food, making vitamins that we don’t make ourselves and protecting us from bad bacteria. “They are interacting with us on a minute-by-minute basis,” he says. Antibiotics fight C. diff with chemicals, but the stool transplant uses a different approach, possibly enlisting the work of good bacteria—those in the feces of a healthy donor—to boost health, a technique that sounds a lot like organic gardening methods that employ good insects to keep bad ones in check.
While a fecal cure may be psychologically unpleasant for the patient, it’s physically so for doctors. Surawicz and her colleague, gastroenterologist Dr. Elizabeth Broussard, prep donor stool in a windowless “soiled utility” room not much larger than a closet. Populated with biohazard bins, the room, on a non-transplant day, smells stale. Donors bring their “deposit” to the hospital in a plastic container. The doctors place the stool in a 1-liter suction canister with a secure lid, then add sterile saline and shake it up. Then they pour the “slurry” through three layers of sterile gauze into another canister, and use a tongue depressor to break up pieces that are still too big and push those through the gauze, repeating until no tongue depressor is required. Then they pull the mixture into syringes to prepare it for the colonoscopy. “Sometimes I stand here and think, ‘What am I doing? I didn’t train for this in medical school!’” jokes Broussard.
With such astounding success in fighting C. diff with stool, doctors and patients are hoping these, and similar efforts to enhance our microbial makeup, such as probiotics, could lead to cures for other diseases. But there is so much hype around the microbiome that some mistakenly believe those cures are at hand. Surawicz fields emails from people looking for a fecal transplant cure for other gut diseases—and even autism—and the Internet is awash in how-to books and videos for DIY fecal enemas (which earn points for resourcefulness, but, given the health risks, are not a good idea).
Happily for future C. diff sufferers—and perhaps others who can be helped with a fresh infusion of gut microbes—stool transplants are likely to be replaced within the next 5–10 years by something simpler and more palatable to patients—most likely a pill loaded with healthy gut bacteria, or possibly a vaccine. Researchers, including Suskind, are also looking at ways of bringing diseases such as Crohn’s into clinical remission with changes in diet alone. “I love my fecal transplant work; for those with C. diff, it’s a phenomenal therapeutic approach,” he says, “but we all can actually change our microbiome pretty easily just by diet alone.” Different types of gut bacteria like to digest different types of foods. Change your diet and you may be able to encourage the good bacteria to grow. (There are data that show diet can put mild to moderate irritable bowel syndrome into remission, and anecdotal experience that remission can be long term.)
For now, the proof is in the fecal transplant patients, an unusually grateful bunch, as evidenced by Dr. Surawicz’s collection of thank-you cards. She sets a few of them out on her office table. One is from a man who lives in Hawaii; another patient hand-painted her card. They tell Surawicz about all the activities they can do that wouldn’t have been possible without her help. “These are the patients who say, ‘You saved my life,’” she says.