- Luke Eastman
One week after celebrating her 80th birthday in December 2015, "Iris" contracted Clostridium difficile, a serious colon infection that causes fever, nausea, severe abdominal pain and debilitating diarrhea.
"It's most unpleasant. You feel lousy and you lose weight," says the Chittenden County resident, who requested anonymity for this story. "It's all bad. I wouldn't wish it on anyone."
C. diff, as the bacterial bug is commonly known, typically is found in and transmitted through contact with fecal matter. It's often contracted in health care facilities by elderly patients or those undergoing long-term antibiotic treatment, which can kill off the digestive tract's "good" bacteria along with the "bad." In Iris' case, she picked up the infection in the community, but was soon hospitalized when her doctor became concerned about her chances for recovery.
And with good reason. The U.S. Centers for Disease Control and Prevention reported that in 2015, nearly a half million Americans contracted C. diff. Of those, at least 15,000 died, though some estimates put the number as high as 50,000. Today, it's one of the leading hospital-acquired infections.
C. diff can be very difficult to treat, especially when patients contract an antibiotic-resistant strain. In Iris' case, she suffered two recurrences in as many months before her gastroenterologist, Dr. Peter Moses at the University of Vermont Medical Center, recommended an unusual treatment: fecal microbiota transplantation (FMT), aka a stool transplant.
Essentially, the process involves using fecal matter from a healthy donor to recolonize the sick patient's colon with benevolent microbes that return it to a healthy state. From the patient's standpoint, the procedure is no different from undergoing a routine colonoscopy.
Some patients recoil at the thought of having someone else's poop squirted into their body, but Iris isn't so squeamish, having worked for years as a medical technologist at what was then called Fletcher Allen Health Care. After researching the procedure online, she agreed to give it a try.
"Everyone has what they call the 'yuck factor,'" she says with a chuckle. "But when you're that sick, you're happy to agree to anything" that offers a potential cure.
- Luke Eastman
Iris' recovery, she reports one year later, was "almost immediate." Her appetite returned quickly and she suffered no ill effects from the procedure itself. Most importantly, the C. diff hasn't returned.
Iris' outcome was typical for C. diff patients treated with FMT, says Moses, who's done this procedure about 100 times. It has a success rate approaching 90 percent, he notes, with minimal side effects and very few reports of serious adverse outcomes. In fact, patients on their deathbeds have been known to recover in several hours after receiving FMT.
In short, shit happens to help some very sick patients. In the eyes of many practitioners, including Moses, FMT is a miracle cure, not just for C. diff but potentially for other gastrointestinal and autoimmune disorders.
He's putting that last hypothesis to the test. Moses is the principal investigator on a Burlington-based clinical trial, overseen by the U.S. Food and Drug Administration, that studies the effectiveness of using fecal transplants to treat patients with mild to moderate ulcerative colitis. This debilitating autoimmune disorder, similar to Crohn's disease, causes inflammation and open sores throughout the colon.
Though ulcerative colitis has no known cure, FMT may hold real therapeutic promise, suggests Dr. Jessica Crothers, a research fellow in UVM's pathology department and one of the researchers working with Moses on the study. As Crothers points out, fecal transplants are only considered a "new" form of therapy in western medicine. In other countries, the practice goes back centuries.
Ancient Chinese texts from the fourth century describe the use of "yellow soup" mixed with human stool to treat dysentery. Similarly, veterinarians have used manure for years as a way to treat livestock with digestive problems.
It wasn't until the 1950s that modern medicine began to recognize poop's potential. In 1958, Dr. Ben Eiseman, then chief of surgery at the Denver Veterans Administration Hospital in Colorado, had four patients suffering from life-threatening enterocolitis, or inflammation of the colon, brought on by prolonged antibiotic use.
Reasoning that he might reboot his patients' digestive tracts with benevolent bacteria, Eiseman gave them enemas of stool obtained from new mothers in the maternity ward. When all four patients recovered, Eiseman published his findings in the journal Surgery, where he suggested that the fecal transplants had "re-establish[ed] the balance of nature" within their guts.
Despite Eiseman's findings, Crothers says, the procedure didn't gain wider recognition until the 2000s, when a hyper-virulent strain of C. diff emerged. Reportedly, some patients desperate for relief began attempting fecal transplants at home using enema bags and turkey basters.
In 2013, the New England Journal of Medicine published the findings of a randomized controlled trial showing that FMT was highly effective in treating recurrent C. diff. In fact, FMT was so much more effective than the standard treatments that researchers halted the study early, considering it unethical to deny the benefits of FMT to patients in the study who weren't receiving it.
Still, Crothers says, the therapeutic use of human waste, something long seen as a source of disease rather than a cure, posed a unique challenge for FDA classification. Is it a drug? A supplement? A biological byproduct?
"[FMT] generated a huge buzz, and the FDA got very uncomfortable with it," she says. In May 2013, the FDA issued a statement that it considered stool to be an "investigational new drug" that required extensive medical trials before it could be used in clinical settings. When this provoked an outcry from the medical establishment, the FDA relented on FMT's use for treating recurrent C. diff, but not for other conditions. Now Moses and Crothers are trying to determine whether FMT is effective in treating ulcerative colitis, too.
Why ulcerative colitis? As Moses explains, it's a fairly common disorder that causes considerable suffering and can even be fatal. Because UC is an autoimmune disorder, he goes on, the cornerstone of conventional treatment is manipulating the body's immune response, which itself puts the patient at increased risk for infection and lymphoma.
There's also a practical reason for trying FMT, Moses adds: The disease always involves the distal colon or rectum, which is easily reached with an endoscope.
UVM Medical Center has been doing fecal transplants for recurrent C. diff since 2014. Early on, Crothers recalls, one of the big challenges was the logistics: As stool is inherently infectious, physicians knew they'd have to screen donors for a variety of diseases, including HIV, hepatitis and rotavirus. But who should pay for such expensive tests? As Crothers puts it, "It all got sticky very fast."
That's when Moses and Crothers discovered OpenBiome, the nation's first stool bank. Sometimes referred to as the "Brown Cross," the Massachusetts-based nonprofit was founded in 2012 by medical researchers who'd watched a friend suffer with C. diff for 18 months before being cured by FMT.
According to the company's mission statement, OpenBiome's goal is to "eliminate the practical barriers" to FMT and facilitate its research by freeing physicians from the hassles of managing a stool-donor program themselves. OpenBiome is now a partner in the UVM study.
"The nurses are psyched because they don't have to handle the poop," Crothers says. "We were buying blenders and had a room converted for blending it. Brown Cross to the rescue!"
OpenBiome extensively screens its donors for various diseases and for hypothetical risks that may be associated with gut health, such as obesity, diabetes and allergies. Only 4 percent of potential donors are accepted — and receive $40 for each "deposit" they make in the stool bank.
Each sample is blended and quarantined for six weeks until it double-tests negative for nasty pathogens, Crothers says. Eventually, the UVM researchers plan to analyze each stool donation for its unique genetic profile.
"We don't really know yet what the ideal donor looks like," she says. "It'll probably turn out that there are different ideal donors for different disease types."
- Luke Eastman
The study of the human microbiome, that amalgam of microbes that dwell in the human body, is still in its infancy. It's estimated that our bodies contain about 10 times as many microbial cells as human cells — literally trillions of fungi, bacteria, viruses and other microorganisms. The vast majority live in the digestive system.
Moses, who's been a gastroenterologist for more than 20 years, says that when he attended medical school, little was known about microbes' role in human physiology.
"That's what's so cool about it for me," he says. "What's emerged over the last five or so years is that we've come to realize how important these commensal passengers that we carry are for good health and how important they are in a variety of disease states."
Indeed, early scientific data suggest that our microbiome plays a role in mood, immunity and various ailments, including migraines, psoriasis and even Parkinson's disease. Moses points out that autoimmune disorders such as Crohn's disease, multiple sclerosis and rheumatoid arthritis have all increased in frequency since the 1950s, coinciding with a drastic rise in the use of antibiotics.
FMT is now being studied as a way to treat conditions once thought to be unrelated to digestive health. In January, a researcher at Arizona State University published the results of a study of children with autism. In it, FMT reduced symptoms involving the children's language skills, social interaction and repetitive behaviors.
"It's fascinating, because you're born with your genes, and, yes, they can be turned off and on, but you can't change the genetic cards you're dealt," Crothers says. "But if you think of your microbiome as an extension of yourself, that's a malleable genetic landscape that you can shift. If we can [adjust] that, the implications are enormous."
Given the severity of ulcerative colitis, Moses and Crothers haven't had to overcome FMT's "yuck" factor with patients they've screened. If anything, they've had to turn away patients who don't meet their criteria. Eight are currently enrolled, but another 12 are needed to complete the study.
As for the results thus far, Moses says the FDA won't allow him to comment on their findings until the study is completed. But if he and Crothers get the results they're expecting, UVM could become the principal site for future FMT trials, opening the door to additional federal funding. And, in the world of medical research, being flush with cash is nothing to pooh-pooh.