Fecal transplant offers rare hope against deadly colon disease

Preparing fecal bacteria
University of Minnesota post doctorate fellow Matt Hamilton prepares bacteria from fecal matter for a transplant surgery at the St. Paul, Minn. campus Nov. 14, 2012. The fecal matter is donated and used to treat patients with Clostridium difficile, an intestinal disease that is caused when a person's gut flora is eliminated by antibiotics.
MPR Photo/Jeffrey Thompson

In an experimental treatment that may be the only way they can save some people who have contracted a dangerous colon infection, out of desperation some Minnesota doctors are transplanting donated human feces into their patients' colons.

Doctors say fecal transplants could allow patients to more quickly develop their own natural defenses against clostridium difficile, an infection that kills 14,000 people in the United States each year, according to the U.S. Centers for Disease Control and Prevention.

The antibiotic-resistant bacteria, which many contract in hospitals, typically are treated with strong drugs. But using the antibiotics can be a double-edged sword, as the drugs also destroy good bacteria that normally keep harmful bacteria in check. If too much good bacteria are lost, the disease can flare up again soon after antibiotic treatment is stopped.

Like many patients who suffer from the infection, sometimes called C. diff, Paula Hanninen's good bacteria had been depleted by her antibiotic treatments.

After spending months in bed battling fatigue, fevers and diarrhea caused by the infection, Hanninen, of Maple Grove, Minn., was desperate for a cure. Too weak to watch her grandchildren, for a time she needed care from her 82-year-old mother.

"To make it to the bathroom was about all I could do during the day," said Hanninen, 63.

Hanninen's medical saga is a classic example of how many patients contract clostridium difficile. After a July 2011 operation on her liver, she developed an infection that required antibiotics. She recovered, but a couple of weeks later returned to the hospital with a high fever. That's when her doctors discovered she had contracted C. diff, most likely during her previous hospital stay.

Microscope counting
University of Minnesota post doctorate fellow Matt Hamilton counts bacteria from a fecal matter sample at the St. Paul, Minn. campus Nov. 14, 2012.
MPR Photo/Jeffrey Thompson

Since then, Hanninen has had more than a dozen recurrent infections, sometimes once a month. Tired of the antibiotic treatments, in late October she was ready to try a different treatment approach -- even though it meant doctors would inject someone else's feces into her colon.

"When you're so sick and you know that there's something there that can make you feel better, you get past that like right now," she said. "That's how I was anyway. I didn't care how yucky it was. I would have eaten it if it would have made me feel better."

In the endoscopy suite, Dr. Mark Larson, the Mayo Clinic gastroenterologist who performed her fecal transplant, snaked a four-foot tube and flexible scope through Hanninen's large intestine. When he reached the end of her colon, he began filling his tube with a brown solution of saline mixed with filtered feces.

"And there we go," Larson said. "Science at the cutting edge, right there."

A OLD, EFFECTIVE TECHNIQUE

Fecal transplants have been around since at least the 1950s. In the early days, doctors would prepare stool enemas for patients with C. difficile. Then antibiotics came along and doctors didn't need to bother with fecal transplants anymore. But antibiotic resistance has changed that, and now the old techniques are being revisited. Nevertheless, 60 years later the procedure is still considered experimental.

Mayo Clinic's fecal transplant program in Rochester is in the very early stages. Dr. Sahil Khanna, a gastroenterology fellow at Mayo who leads the program, has arranged about a dozen transplants in the past few months.

"So far we haven't seen any problems or complications to stool transplant," Khanna said. "It seems to be a very low-risk, well tolerated procedure as has been documented all over the literature and that's been our experience here also."

Consulting with doctor
Paula Hanninen, 63, Maple Grove, consults with Dr. Sahil Khanna of the Mayo Clinic before her fecal transplant in Rochester, Minn. Oct 30, 2012. Hanninen contracted Clostridium difficile shortly after being given strong antibiotics to treat a complication from a liver surgery performed at another hospital. She has battled about a dozen recurrent C. difficile infections in the past a year-and-a-half. During that time she was too exhausted to babysit her grandchildren and she spent many days just lying on her couch.
MPR Photo/Lorna Benson

Of the more than 500 cases reported in the medical literature worldwide, fecal transplant success rates range from 85 percent to more than 95 percent, Khanna said.

Reached by phone a few weeks after her transplant, Hanninen said she has no sign of a recurrent infection. She has resumed many of the activities she had previously put on hold, including her daily workouts.

Yet for all its simplicity in concept, a fecal transplant can be complicated to execute. Hanninen had to find her own stool donor. Her adult son volunteered. That meant that on the morning of her transplant he had to provide a fresh stool sample for her. He also had to be tested for numerous infections and diseases to make sure he was healthy enough to donate feces.

That's far from ideal, said Dr. Alexander Khoruts, a gasteroenterologist at the University of Minnesota who aims to make the fecal-transplant process more efficient.

"Having done a couple of these personally I decided this is not a way to do this on any kind of a scale," he said.

"KIND OF LIKE A COOKING SHOW"

Khoruts, who has performed more than 100 stool transplants since the university started its program in 2009, now relies on a donor program that supplies processed feces so his patients don't have to find their own donor. Two male donors, who are tested regularly for infections and diseases, supply the university with all of the feces that it needs for its transplant program. The men don't get paid for their donations.

Because the stool is processed and frozen, Khoruts said, there are fewer problems coordinating transplants for patients.

Fecal bacteria sample
University of Minnesota post doctorate fellow Matt Hamilton displays a sample of fecal bacteria at the St. Paul, Minn. campus Nov. 14, 2012. The fecal matter is donated and used to treat patients with Clostridium difficile, an intestinal disease that is caused when a person's gut flora is eliminated by antibiotics.
MPR Photo/Jeffrey Thompson

"We still occasionally employ fresh stuff, but we haven't found that the frozen is any different," he said. "So most of it is now done with frozen material."

The frozen stools are processed in a lab at the university's St. Paul campus, where research assistant Matt Hamilton weighs the fresh feces on a scale. He then scoops the material into a blender and adds saline to dilute it.

"It works kind of like a cooking show here, where I add a little bit of this and add a little bit of that, turn the blender on," said Hamilton, a post-doctoral candidate in diagnostic and biological sciences.

It only takes a minute or so to blend the feces. When the process is finished, Hamilton passes the material through several sieves to remove undigested food particles. He pours the remaining solution into small bottles and places them in a centrifuge for about 15 minutes to separate the healthy gut bacteria from the saline.

When the centrifuge stops, Hamilton places a small sample of his material on a microscope slide. He adds a fluorescent dye that sticks to DNA and he begins counting the bacteria.

Hamilton plugs his final numbers into a spreadsheet to see how much bacteria he has collected. That's how he determines how many doses he will have for patients.

"We started with 150 grams, we end up with three treatments for patients," he said.

The whole process takes several hours, but University of Minnesota researchers believe the effort is key to taking fecal transplants mainstream.

Microbiologist Michael Sadowsky, who oversees the lab, said researchers are concentrating on making stool transplants more efficient. But he hopes they develop more user-friendly products, like pills, to treat C. diff.

"You might want to think of this as how we've progressed with probiotics over the years and how it went from drinking kind of nasty things to inclusion of these microorganisms in food, for example," Sadowsky said. "And once we understand more about these microbes and which ones are important for this process, those types of products could eventually be made. So this is an intermediate step."

NOT FDA APPROVED — YET

In the meantime, the university has federal Food and Drug Administration permission to begin clinical trials on its fecal transplant solution. But first it must raise the money to begin the trials.

Because the FDA has not approved fecal transplants, some insurers may not cover the cost. At the university, fecal transplants coincide with a colonoscopy, which is often covered by insurance. The university currently does not charge for its donor screening program or preparing the fecal materials.

Mayo Clinic officials say insurers have so far paid for the transplants it provides. Mayo does ask fecal donors to be screened by their own physicians. Those charges may or may not be covered by insurance.