Mysteries of the Microbiome

A U of M associate professor explores the complex world of human microorganisms and the cures they may hold

C. diff exists in both spore and bacteria state. Antibiotics will kill the bacteria but leave the spores, which turn back into bacteria and re-infect the host. This is why antibiotics can have a hard time killing it.

Our gut flora, and possibly the biofilm that protects it, gets worn away with repeated antibiotic treatments until there's no good bacteria left. Here C. diff thrives, and the victims wind up like Catherine Duff.

"In 2009, I had a patient that was quite desperate," Khoruts says, explaining the case that got him written up in the New York Times a year later, helping bridge the way to wider acceptance. "She arguably was more desperate than Catherine."

Hadza hunter-gatherers have vastly different gut bacteria, which is why Jeff Leach is preserving stool samples for study
Human Food Project
Hadza hunter-gatherers have vastly different gut bacteria, which is why Jeff Leach is preserving stool samples for study

Khoruts spent seven months treating her with antibiotics, to no avail. So the 49-year-old doctor went back almost a quarter-century to something he heard about back in his first year of med school — fecal microbiota transplantation (FMT). It has been done throughout history and was first attempted in the U.S. in 1958. But perhaps unsurprisingly considering its negative associations, FMT didn't come into widespread practice.

FMT remains an experimental treatment, and Khoruts had to fill out an FDA application that took at least six months to complete and in the end weighed 22 pounds. Khoruts took a stool donation from the woman's husband and had all the microbiota in it sequenced and judged safe before he reseeded her lower intestine, using the same device one would for a colonoscopy.

Not only did the procedure cure her, but subsequent testing proved that her husband's microbiota had successfully inhabited her damaged gut and driven out the C. diff. It was the first documented case in history, mainly because DNA sequencing technology has become affordable only in the last half-dozen years.

Recently a doctor in Canada revealed he'd successfully treated 27 people with poop pills. The pills are simply donor feces encased in gelatin, so it survives your digestive tract. The patient needs to swallow two to three dozen of them.

"Pill or as a colonoscopy, those are little questions and kind of technical challenges," says Khoruts.

In Europe, where colonscopy is rare, this treatment is typically accomplished through nasogastric tubes passed from the nostril to the stomach, another option he considered.

"I went through the mental checklist how am I going to do this," Khoruts says. "My nightmarish image was we infuse this in her stomach and she vomits and aspirates. Then I'm telling how it happened in a courtroom somewhere."

Despite Khoruts's well-publicized operation a year earlier, Duff had great difficulty finding a doctor in her area willing to perform the procedure.

Naturally there's a substantial ick factor, but on the other hand, there's never been a reported complication, and from a medical standpoint, it's mind-bogglingly cheap. The average colonscopy costs less than $1,200, not counting the cost of sequencing the donation material. Preparation requires little more than a disposable blender. Meanwhile, Duff calculated that her insurance paid $275,000 a year for her Vancomycin (antiobiotics).

"Finally, my husband — who is a retired submarine commander and has spent four months at a time under water in a metal tube with 180 guys and is grossed out by nothing — said, 'Let's do it at home,'" Duff recalls.

Her gastroenterologist at least obliged to test her husband's contribution (it was fine), then gave them some enema bags and wished them luck.

The cure took little time to work its magic.

"Literally the next day for the first time in months I got up, took a shower, got dressed, and went downstairs," Duff says.

A Dutch study comparing antibiotics to FMT in treating severe C. diff had to be stopped because the antibiotics patients were faring so poorly. The study, published in Nature, suggested that FMT has a success rate of over 90 percent compared with under 30 percent for antibiotics.

Only in the last year has the practice become widespread enough that scam artists have stepped in. They're charging as much as $20,000 for the procedure, taking advantage of people's desperation and the paucity of doctors willing to do it.

After some initial hesitation and scrutiny of the burgeoning field, this summer the FDA cleared doctors to undertake the procedure without filing the aforementioned 22-pound Investigational New Drug application with the FDA. However, FMT is still considered an experimental procedure, and some insurance companies won't cover it (those that do bill it as a colonoscopy).

Meanwhile, Khoruts and the University of Minnesota have streamlined the process. They've developed a pool of well-screened, healthy donors and own a vault full of filtered, frozen, odorless samples for future use both in transplants and studies.

"The real solution is to move this thing forward and standardize it," says Khoruts. "Make it like anything else in medicine that you can feel comfortable about."

Ellen Bolte was the first to postulate a link between autism and gut bacteria, in 1996. Bolte is a self-taught computer programmer in Chicago with a year of community college education. She delved into medicine only when her youngest child, Andrew, developed autism.

At the time, autism was believed to be a genetic disease. Bolte suspected otherwise, because up until her son was 15 months old, he was happy and healthy. That was when Bolte's pediatrician moved out of state. Around the same time, Bolte switched Andrew from soy milk (the pediatrician's preference) to cow's milk.

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