The Enema of Your Enemy is Your Friend
Fecal transplants could be a cheap and effective treatment for gastrointestinal disorders.
Evidence has been accumulating for years that gut infections can be treated by introducing beneficial bacteria. A reliable source of healthy bacteria may be healthy people’s feces. Two years ago, Emily Walker explained how and why fecal transfer may cure stubborn and painful Clostridium difficile infections. This week, the New England Journal of Medicine published the best support for the treatment yet: In a randomized, controlled trial, antibiotic treatment cured 31 percent of patients, while fecal transplant cured 94 percent. The original article is below.
One day in 2008, Ruth, a Long Island teacher, walked into her doctor's office with a container of a relative's feces, lay down, and had her doctor pump the stool inside her. Ruth had been suffering for nearly two years with an intestinal infection called Clostridium difficile, which caused her to suffer from excruciating diarrhea. She had lost 20 pounds. Her hair was falling out. Friends asked if she had cancer.
Then she met Lawrence Brandt, a gastroenterologist at the Montefiore Medical Center in the Bronx who believed he had developed a procedure to cure people of recurrent c. diff infections: fecal transplant. Brandt has been inserting feces into his patients for a decade now and claims to be solving their problems nearly 100 percent of the time. If his method really works—and he's not the only doctor who believes that it does—then we may have found a viable, if weird, solution to a serious problem. C. diff infects 250,000 Americans each year and killed more than 20,000 from 1999 to 2004. (Researchers estimate that 13 out of every 1,000 patients admitted to a hospital will pick up the bug.) Antibiotics will always be the first response to such infections, but when those fail, a fecal transplant could be the next step. For Ruth, at least, the procedure was a godsend. "I'm cured," she said. "Period. End of story. Cured."
Here's the basic idea. People suffering from the hardy C. diff bacteria are generally prescribed a powerful antibiotic. Problem is, the drugs don't just kill the invaders; they also wipe out much of the beneficial bacteria in the gut. With these "good" microorganisms out of the way, any C. diff stragglers have a much easier time regrouping for a second bout of illness. If there were some way to respawn the beneficial bacteria in the intestines, such re-infections could be warded off. Some people, like Ruth, turn to expensive probiotic supplements. (At one point she was spending $350 on them every week.) But in certain cases, a patient who has lost nearly all of her good bacteria will find it nearly impossible to get them back. A fecal transplant seems to work as a sort of mega-probiotic, allowing doctors to repopulate a patient's intestines with the appropriate microorganisms by placing a robust sample directly into her gut.
Doctors recommend that the fecal donor be someone close to the patient—a family member, perhaps, or a spouse. Scientists reason that when people live in close quarters, they are exposed to similar bacteria—good and bad—and are likely to have had a similar set of bacteria living in their guts before anyone got sick.
The donor takes a stool softener the night before and then gives a full morning bowel movement to the recipient, who takes it to a doctor for screening. It's important to make sure that the sample doesn't contain any parasites or other pathogens, such as hepatitis, salmonella, or HIV. Once the transplant material has been cleared, the doctor mixes it with saline to make about a pint of liquid with the consistency of a milkshake. This is pumped into the patient's colon using a colonoscope or endoscope, or siphoned into the stomach via a nasogastric tube. (The latter method is considered more dangerous, since there's a chance feces will end up in the lungs. Colonoscopies carry their own risk of bowel perforation.)
And then there's the do-it-yourself crowd. All you need is a bottle of saline, a 2-quart enema bag, and one standard kitchen blender. Mike Silverman, a University of Toronto physician who wrote up a guide to homespun fecal transplants for the journal Clinical Gastroenterology and Hepatology, says it's entirely safe to do the procedure this way, provided that a doctor gets involved at some point to screen the donor sample. He felt he needed to draw up the instructions because administrators at his hospital wouldn't allow their doctors to perform a procedure that hasn't been validated in a large, peer-reviewed study.
It's true there's been no major clinical trial of fecal transplants, but the procedure appears in the medical literature at least as far back as 1958. That's when a Denver-based surgeon named Ben Eiseman performed four of the procedures to rid patients of a form of colitis thought to be caused by C. diff. His plan was to administer "normal feces into the colon of patients with the disease," so as to "re-establish the balance of nature." Three of his four patients were near death before the fecal enema. After, they recovered. This small experiment suggested a "simple yet rational therapeutic method," Eiseman and his colleagues wrote, that deserved careful evaluation.
Now we're beginning to see some more extensive studies. Mark Mellow, a gastroenterologist at INTEGRIS Health in Oklahoma City, recently presented a paper showing that 15 out of 16 C. diff patients whom he'd provided with a fecal transplant remained disease-free after five months. Several other papers presented at the meeting showed similar positive effects, and in every case, symptoms disappeared almost immediately after the transplant.
Still, the evidence supporting fecal transplant comprises just about 20 published case reports involving about 200 patients. Until a large-scale, randomized trial is published in a big-name medical journal, most doctors will likely follow the example of the University of Toronto and hold off on performing the transplant. Indeed, relatively few gastroenterologists have even tried it. Colleen Kelly, a gastroenterologist at Women & Infants Hospital of Rhode Island, surveyed 72 gastroenterologists at a recent international medical meeting and found that only seven had performed the procedure. Nearly half said they'd be willing to perform a transplant on a sick patient, but the rest said they weren't ready yet. "I really think in another couple of years, it's going to be something that everyone's doing," said Kelly, who has performed the operation 22 times herself.
Infectious-disease experts are a little more tempered in their enthusiasm. According to Vincent Young of the University of Michigan, the data look promising but he wouldn't perform a fecal transplant himself because there are too many unknowns about what bad things might be lurking in a stool sample. William Schaffner, president of the National Foundation for Infectious Diseases, warned that the procedure is still in its early days and not yet ready for prime time. (The American College of Gastroenterology, for its part, has no official position on fecal transplants.)
But the true believers have even bigger plans. They hope fecal transplants might be used to treat other gut-related conditions, such as ulcerative colitis and even obesity. Some very overweight people, for example, are thought to have more of a certain type of bacteria in their intestines, which causes them to extract extra calories from complex carbohydrates. With this in mind, researchers found that fat mice would lose weight if transplanted with feces from thin ones. Later, a team of Dutch researchers tried the same approach in humans: No one lost weight, but the fecal recipients did show a significant improvement in their ability to regulate insulin. (That study is under review and should be published in the next few months.)
For all its promise, it's unlikely fecal transplants will take off any time soon. Not because patients are grossed out by the procedure—in fact, doctors say that long-standing sufferers from C. diff are eager to have it done—but because there's so little funding for large-scale clinical trials. Drug or medical-device companies usually foot the bill for such research, but in the case of a natural, patent-free treatment like this, no company stands to turn a major profit. If anything, fecal transplants would end up costing the pharmaceutical companies money: A single pill of vancomycin—one of two antibiotics used to treat C. diff—costs about $55, and the average dose is four pills daily over a two-week stretch. A glass of shit, on the other hand, costs very little. That doesn't mean we'll never get the much-needed data: Lawrence Brandt, the gastroenterologist in the Bronx, is applying for a grant with the National Institutes of Health for a small, double-blind, controlled study. He says he'll need about 40 patients, and he's hoping to get started right away.
Emily P. Walker is Washington correspondent forMedPage Today.
Electron micrograph image of c.diff bacteria by CDC Public Health Image Library.