An Experimental Therapy from the “Bottom Up”

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Are we flushing away cures? In the last few years, physicians have developed a new respect for what used to be considered waste. Led by a maverick Australian physician, many US doctors have begun to test the curative capacity, when appropriately acquired, prepared and administered, of human excrement.

For once, it’s not the fiber that interests these digestive specialists; it’s the creatures that live in it, the intestinal flora. These indwelling microbes, when compared cell-to-cell, outnumber their hosts by about 10 to one. More than 1,000 different strains of bacteria co-exist peacefully in the typical healthy bowel. But when the delicate balance is altered by antibiotics or other causes, a few strains can become dominant, leading to severe diarrhea, inflammation, tissue damage, even death.

Bacterial aggregates derived from fecal matter have been used sporadically to treat digestive disease for more than 50 years. These were often last-ditch efforts aimed at restoring microbial balance for patients with raging intestinal infections. Fecal microbiota transplantation (FMT) – also known as fecal bacteriotherapy, among other names – is designed to calm a troubled bowel by reintroducing the vast diversity of collaborative bowel inhabitants after the usual, collegial mix has been disturbed.

The first FMT cases, dating back to 1958, were used to treat life-threatening infections caused by aggressive bacteria that had overwhelmed the bowel and eradicated the competition. When antibiotics were unable to control the infection, physicians were able to restore balance by collecting fecal matter from a healthy donor and injecting it into the patient’s colon. It was like a massive dose of probiotics, but delivered bottom up, rather than top down.

More recently, the approach has produced lasting remissions for a small number of patients with a common disease: ulcerative colitis. In 2003, a team led by the Australian physician, Thomas Borody, published a report [pdf] on successful treatment with this approach of six patients who had longstanding ulcerative colitis (UC). “Complete reversal of UC was achieved in all 6 patients following the infusion of human fecal flora,” the authors reported. “These 6 cases document for the first time the total disappearance of chronic UC without the need for maintenance treatment.”

After interviewing Borody, the Freakonomics podcast summarized the expanding medical role of human feces like this: “To paint it with a very broad brush: it could be that many maladies – from intestinal problems to obesity to disorders like multiple sclerosis and Parkinson’s and Alzheimer’s and perhaps even cancer – are related to damaged or missing gut bacteria; the solution therefore may lie in transplanting healthy bacteria into a sick person.”

“This is a fascinating idea, and the early studies show great promise,” said University of Chicago gastroenterologist David Rubin, associate professor of medicine. The notion has also made headway among patients. “We are getting at least one phone call a week from patients asking about the treatment and when we are going to start treating patients,” said colleague Stacy Kahn, instructor of pediatrics at the University of Chicago.

Although fewer than a dozen case reports involving ulcerative colitis have been published, Rubin and Kahn realized that many more patients were getting treated, largely without supervision or medical oversight, a development they called “alarming.” Several websites now provide guidance, almost like recipes, on how to perform this relatively simple procedure.

“This morning I decided to try a fecal transplant,” begins the saga of “Lucky Lindy,” posted on HealingWell.com. “I’ve been reading about it for months, and figured I might as well try … and while the process was a little gross it was easier than I anticipated. For anyone who is interested (and not grossed out), below is the process I used.” He goes on to list his entire protocol, with daily progress updates and cost-cutting tips, such as using a fork to stir the broth instead of a difficult-to-clean blender.

Although a lot of patients with ulcerative colitis were interested, “We found that no one had looked at the social issues surrounding fecal transplantation,” said Rubin. “Before we offer this, we wanted to find out how patients understood the process and take a look at the ethical issues that could also be raised by this therapy.”

Rubin, Khan and research project manager Rita Gorawara-Bhat organized six focus groups in 2009-2010 with patients or parents of children with ulcerative colitis to “explore the attitudes and concerns” raised by this approach. They published their findings in the June issue of the journal Inflammatory Bowel Disease.

They found that 21 out of 22 patients or parents of patients were interested in trying FMT for themselves or their child. Most wished it were already available. They viewed the treatment as more ‘natural’ than using drugs to control the disease, and easier and safer than currently available therapies. Many compared it to probiotics, a popular alternative therapy among patients with colitis.

“Although initial distaste/disgust and ‘yuck factor’ were uniformly mentioned when discussing FB, these concerns were outweighed by perceived benefits,” the authors wrote. “Participants routinely stated that living with the disease was far worse than any treatment and had changed their tolerance for therapies that others might consider unacceptable or unpleasant.”

The major concerns were focused on how donors would be selected and screened. Patients wanted healthy donors, usually family members, and asked that even their diet and medications be considered. A donor who had eaten peanuts recently, for example could be hazardous for a recipient with peanut allergies.

Physicians recommend a workup similar to that of an organ donor, with careful screening for multiple pathogens, including HIV, hepatitis and other viruses, as well as various parasites and worms.

Patients and parent were comfortable with the idea of a “spray” colonoscopy or delivery via enemas, but were disturbed by the idea of using a naso-gastric tube for the transfer of fecal bacteria, although this method has been used to treat Clostridium difficile infections.

“What our study ultimately tells us is that patients are not only tolerant of this therapy but are eager for it to become available,” Rubin said. “A few have already tried this strategy at home, using ‘protocols’ they found on the internet and tools available at any drug store.”

“We hope to begin offering FMT this fall,” he said, “in a carefully controlled, clinical-trial setting.”

There are many things we do not yet know about the risks and benefits of FMT, the authors agreed. The safety of such a treatment and broader implications of risk remain unconfirmed, so careful preparation and more study is necessary before this can be offered to patients with ulcerative colitis.

“Many patients do benefit from proven traditional therapies,” Rubin said, “which should always be considered before experimental treatments, no matter how attractive they may sound.”

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Kahn SA, Gorawara-Bhat R, & Rubin DT (2011). Fecal bacteriotherapy for ulcerative colitis: Patients are ready, are we? Inflammatory bowel diseases PMID: 21618362

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