IN THE LATE 1950s, A DENVER SURGEON named Ben Eiseman saw four patients who were dreadfully ill with recurrent diarrhea caused by antibiotics, which had obliterated the friendly bacteria in their gut, leaving them vulnerable to infections by pathogenic bugs. No treatments had helped. Eiseman decided to try something new and more than a little bizarre: infusing their colons with a slurry of feces from donors. His hope was that the healthy bacteria that typically make up about half of stool would colonize the patients’ intestines and overpower those that were making them sick.

These were modern medicine’s first “fecal microbiota transplants,” or FMTs—and they worked. Eiseman’s patients had what’s now known to be an overgrowth of the bacterium Clostridium difficile, a condition that can develop after taking antibiotics. But the 1960s brought new drugs—other antibiotics—that successfully treated C. diff. (as it is routinely abbreviated by physicians), and it would be another half century before Eiseman’s unconventional approach took off in earnest. For George Russell, in 2010, FMT was a treatment of last resort for a two-year-old patient at MassGeneral Hospital for Children who had suffered from C. diff.throughout her young life. “Every time we got her off antibiotics, she was sick again,” says Russell, a pediatric gastroenterologist who is now at Boston Children’s Hospital. “We were faced with removing her colon or putting her on antibiotics for literally years.” Instead, encouraged by reports of success by other physicians, Russell tried a fecal transplant. “In 24 hours, she was completely well,” he says.

That’s also what happened to virtually all of the subjects in a recent study conducted by Josbert Keller of Haga Teaching Hospital in The Hague, Netherlands, and several of his colleagues. The results, published last year in The New England Journal of Medicine, showed 15 of 16 cases of C. diff. infections clearing up after one or two treatments with FMT. In that clinical trial, the patients received donor feces via a nasoduodenal tube snaked from the nose into the upper part of their small intestines. (FMT can also be administered during a colonoscopy directly into the lower intestine or colon.) The control group received oral vancomycin, a standard treatment for C. diff. that cured less than a third of the patients, and FMT proved so dramatically superior that the authors stopped the study and gave fecal transplants to the control patients too.

Other research has shown similar results, even in those who have had repeated rounds of vancomycin. And C. diff. is desperately in need of a cure. Just in the United States, there’s an annual tally of more than 300,000 cases, with some 14,000 people dying from the infection each year. C. diff. symptoms can trap patients at home with profuse diarrhea, intense abdominal pain, weight loss, fever and loss of appetite.

Now clinicians and scientists are wondering whether FMT might also work for Crohn’s disease, ulcerative colitis, other bowel conditions and even disorders such as autism that may have a gastrointestinal component. But FMT isn’t yet standard treatment even for C. diff. infection. And while the Food and Drug Administration did recently allow it to be used by physicians  for that indication, it classified FMT as an “investigational new drug” if used to treat other conditions—a high bar for research because of the expense and logistics of ushering the treatment through the many steps of FDA review. As a result, a do-it-yourself culture has emerged in which people afflicted with debilitating diseases arrange treatments on their own.

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WHILE IT’S NOT YET ENTIRELY known why fecal transplants are so effective in treating C. diff. infections, a large part of the answer may be that introducing donor feces into a patient’s gut changes the makeup of the recipient’s “microbiome”—the complex, distinctive array of bacteria, viruses and other microorganisms that live on and inside humans, chiefly in the gastrointestinal tract. These 100 trillion microbial passengers are connected to health in myriad surprising ways, affecting the immune system and mental health as well as digestion and even body composition.>

In the case of C. diff., bacteria that arrive through FMT may overwhelm the pathogen, taking over its biological niche, says David Suskind, a pediatric gastroenterologist at Seattle Children’s Hospital. Bacteria live in complex ecosystems, with each species having its own niche in that system. The theory is that with the introduction of healthy donor bacteria, C. diff. may no longer be able to thrive, because the new species have taken its place in the gut ecosystem. Or perhaps C. diff. creates an imbalance in the gut flora that the arrival of donor feces somehow corrects. In the Dutch study, when researchers analyzed the microbial species in patients’ intestines before and after the treatment, they documented distinct changes, with a more diverse mix of bacteria post-FMT as well as some species that had decreased in number. Other research, too, has noted an increase in the diversity of species in the gut flora after FMT. It could even be something about the donor feces other than the bacteria, perhaps positive effects produced by the molecules they secrete.

Even without knowing exactly how fecal transplants work, there seem to be few worries about safety—at least for treating C. diff. Doctors who’ve used the procedure haven’t seen many problems, and the results of studies that have looked at patients for up to six months post-procedure have been encouraging. Getting the nod from the FDA has also helped, and word seems to be getting around that this can be a reasonable approach for treating an otherwise intractable condition.

COLONOSCOPY IS CURRENTLY THE MOST COMMON approach for administering FMT in the United States, and so for patients, getting the treatment is normally no more difficult—and no less inconvenient and uncomfortable—than that procedure. However, it’s not medically trivial. And potential donors have to be screened for transmittable diseases, a family history of autoimmune diseases or digestive issues. Once a suitable donor is found, patients do the standard colonoscopy prep, with fasting and laxatives, and they may also receive a course of antibiotics to clear out as many of the existing gut bacteria as possible. The colonoscopy is performed while the patient is sedated. Colonoscopes have channels for medications or tools, and a physician simply squirts in the fresh donor feces.

Still, there are ways around some obstacles. In a 2012 study, Alexander Khoruts, a gastroenterologist at the University of Minnesota in Minneapolis, reported ways of overcoming some of the aesthetic barriers and cost considerations. He and his colleagues showed that the FMT microbes can be extracted from donor feces and frozen, with no apparent lack of efficacy, and that the donor-selection process can be rigorously standardized. And this past June, Elizabeth Hohmann, an infectious disease specialist at MGH, and her colleagues published the results of a study in which administering frozen feces via a nasogastric tube for recurrent C. diff., which requires less preparation, compared favorably to using colonoscopic administration.

Now Hohmann’s group is looking at how to encapsulate frozen feces in pill form. That could solve several logistical problems at once. “You would have to take about 15 pills over two days,” says Hohmann. “They’re the size of a large vitamin. It takes 10 minutes, total.” The capsule is specifically designed so that the pills don’t release their contents until they have passed through the stomach, which is acidic, and reach the small intestine, where the alkaline environment dissolves the capsule. Hohmann and her colleagues submitted their results to a major journal after treating 20 patients with this approach.

Hohmann’s team has also developed an exacting screening protocol. The FDA, in approving FMT for C. diff. infection, recommended that donors be tested for a variety of bacterial and parasitic pathogens in their stool; that they have normal results on standard laboratory screening tests such as lipid profile, liver function and complete blood count; and that their blood be screened for HIV and hepatitis A, B and C. But Hohmann goes further, ensuring not only that donors are completely healthy, with no medical problems or family history of intestinal problems, but also that they are not obese nor overly thin, do not have any indication of diabetes or insulin resistance, and harbor no other inflammatory conditions. “So many of those issues are potentially linked to the microbiome,” she says.

Once potential donors complete an exam and have had all of the necessary blood work, the stool samples can be collected over time and frozen, then processed into liquid form to be given by nasogastric tube or colonoscopy or into capsules for oral administration. And because the collected feces aren’t transplanted immediately, there’s time to rescreen donors to make sure they weren’t incubating important infections not caught by the initial tests.

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ANY IMPROVEMENTS TO THE PROCESS OF FMT seem destined to help it become increasingly common for treating C. diff. infections, if only because it works so much better than any other option. Meanwhile, interest in other applications is also growing, despite the FDA’s decision to require a full series of clinical trials for other uses. Whereas a doctor who wants to give a fecal transplant for C. diff. infection need only get a patient to sign a consent form, those who want to start a trial for Crohn’s disease or ulcerative colitis now have to fill out a raft of paperwork to get FMT reviewed as an investigational new drug, or IND. But that hasn’t stopped clinical studies from springing up all over the country.

David Rubin, a gastroenterologist at the University of Chicago, is studying FMT for ulcerative colitis, while David Suskind at Seattle Children’s Hospital is enrolling patients for a study looking at FMT in children with Crohn’s. Both ulcerative colitis and Crohn’s disease are types of inflammatory bowel disease, or IBD. Suskind’s interest was kindled when a patient who received FMT for C. diff. infection also had her IBD go into remission. “I started wondering, what is the role of the microbiome in IBD,” Suskind says. “There is quite good basic science showing that an imbalance of gut bacteria occurs in the GI tract of people with IBD.”

With that in mind, he is currently conducting a study to look at the safety and efficacy of FMT for Crohn’s disease in his pediatric patients. His approach starts with a cleanout of the intestines, similar to a colonoscopy prep, as well as a short course of antibiotics, both designed to help rid the gastrointestinal tract of any possible pathogenic bacteria and provide a kind of clean slate for the new microbes. He chose to use a nasogastric tube to administer the feces directly into the small bowel, reasoning that this area is more affected by Crohn’s than the large intestine. The results so far have been “very positive,” he says. His first patient, who just happened to walk into the office the day he got the approval to start enrolling the study, had Crohn’s that had proven difficult to control. He had been on multiple medications over many years, and the disease was flaring up despite ongoing treatment. “Going into the transplant he was having abdominal pain and cramping, poor weight gain and six watery stools a day,” says Suskind. “At the two-week follow-up, he had gained four pounds, was having no pain and had two formed stools per day. All of his lab numbers had improved as well. He’s continued to do quite well.”

Although Suskind says this was one of the most dramatic improvements he saw, other patients have also done well, and he has been encouraged enough by the results that he is planning a double-blind placebo-controlled trial of FMT (in the first study, all of the patients knew what treatment they were getting). Each patient will receive a nasogastric tube, and the person performing the transplant will introduce either a placebo of saline solution or FMT.

Rubin is studying FMT for a different kind of inflammatory bowel disease—ulcerative colitis, or UC. He is focusing on patients with a comparatively mild form of UC to be sure that they can tolerate the treatment and because he suspects that those with more severe forms of the disease may be harder to treat with FMT—and that it could carry higher risks for those patients.

Both Rubin and Suskind believe there are more complex factors at work in those who have inflammatory bowel disease than in patients with C. diff. infections—and so FMT may not work as simply and dramatically in those cases as it does for C. diff, which is the result of an overgrowth of just one bacterial species. And while it’s clear that the immune system plays a role in IBD, it can be difficult to know whether immune system problems are causing the imbalance in gut flora or whether it’s the other way around. If the immune system itself is driving the disease process, problems might recur, suggests Rubin, and it could be necessary to do repeated FMTs to achieve lasting improvement.

There could also be safety concerns about using this therapy for more complex conditions. “Our general feeling is that FMT will be shown to be quite safe and well-tolerated,” says Suskind, ”but we have to be cautious and prove that before it becomes widely used. If we’re going to be treating an autoimmune disorder such as Crohn’s disease with FMT, for example, that means that hypothetically, you could cause an autoimmune disorder with it, too.”

Meanwhile, as the FDA tries to regulate how the medical community uses fecal transplants, many patients, desperate for relief from debilitating symptoms, are trying to self-administer treatments. “One concern is that if the FDA makes it too hard for doctors to give FMT, patients are going to do it themselves,” says Brown’s Colleen Kelly. “There are even YouTube videos out there. People find their own donors and do it with home enemas.”

That trend only amplifies worries about safety, of course. But as more results from clinical trials come in, it should become clearer whether FMT can be effective for disorders other than C. diff., and how best to administer the treatment and at lowest cost with maximum benefit. Along the way, scientists hope to learn more about the workings of the complex ecological community made up of trillions of bacteria in the gastrointestinal tract. But for now, it’s exciting that something so simple and ubiquitous holds so much promise for healing the gut.