In Future Fecal Transplants, "The Tool Won't Be Stool"

http://www.kqed.org/.stream/anon/radio/science/2015/06/Science_fecal_transplants.mp3
Seven years ago, a patient asked Neil Stollman, a gastroenterologist in Oakland, to do something so “absurd,” he says, he was tempted to turn her down immediately: to transplant feces from one person to another, using a colonoscopy tube.

“I said, 'No. What, are you crazy? I’m not putting poop in someone’s tush,'” recalls Stollman.

Still, Stollman had to admit it wasn’t an entirely crazy idea.

The patient had C. diff, a disabling intestinal infection that kills about 15,000 people a year. C. diff is often picked up in hospitals or after heavy rounds of antibiotics.

C. diff is caused by bad bacteria in the gut. So, Stollman says, once he "got over the absolute ick-ness of it," it seemed logical that you might cure C. diff with good bacteria donated from a healthy person. The easiest place to find millions of live human gut bacteria? Poop.

The transplant worked. Stollman’s patient was cured.

Today, fecal transplants are widely accepted as an effective therapy for C. diff.

A handful of companies, including the Massachusetts-based Open Biome, have sprung up to try and make the procedure more palatable, by providing pre-screened donor poop, or frozen poop pills that obviate the need for the tube. Meanwhile, about 70 clinical trials are in process to see what else fecal transplants might cure, but researchers say they haven’t seen the kind of slam dunk effect they do with C. diff.

And some researchers -- including Stollman -- say there’s got to be a better method, even for C. diff.

“This is a community of hundreds to thousands of species of microorganisms, so there’s just so much about it that we don’t understand,” says Justin Sonnenburg, a Stanford researcher and author of The Good Gut: Taking Control of Your Weight, Your Mood, and your Long Term Health.

Sonnenburg calls fecal transplants a kitchen-sink approach. Rather than pinpointing specific bacteria in the patient’s gut, the transplant largely replaces it with trillions of live bacteria, many of whose functions are still unknown. They could make the patient sicker.

And remember, they’re alive. The whole idea of dosage kind of flies out the window.

“You have no idea what the life span of this microbe is going to be in that person's gut,” says Sonnenburg. “It may be there for the rest of their life.”

In South San Francisco, a company called Second Genome is looking for a way around that problem.

CEO Peter DiLaura opens a freezer full of glass vials. They’re samples of poop, naturally, but also samples from other microbial communities, such as the bacteria and other organisms that live on our skin.

Second Genome collects samples from hundreds of people with specific diseases, like for example, inflammatory bowel disease, or IBD.

Using $100,000 Illumina gene sequencers, researchers scan the patients' microbiota to look for commonalities. Perhaps some bacteria are more prevalent, or conspicuously absent, in people who have the disease.

The next question, says DiLaura, is what those specific bacteria are doing.

“What are they secreting? And how do the things that they secrete affect the human biology of that disease?”

Maybe there are chemicals out there that could target -- actually zero in on -- those specific bacteria.

The goal is a drug that blocks the damaging effects of the microbiome in inflammatory bowel disease. Second Genome's first drug is currently in Phase 1 clinical trials, which are designed to show whether a product is safe. Subsequent phases, in a process that could take several years or longer, test for efficacy.

Unlike antibiotics, which kill bacteria largely indiscriminately, these drugs would feed certain bacteria and starve others. And because there’s no actual, live bacteria involved, there’s less of a concern about dosage.

If it works, says Dr. Neil Stollman, in Oakland, one day in the not-so-distant future, “the tool won’t be stool.”

That is, live poop might eventually be replaced with something a lot more like a pill. Inert. Odorless. Something the FDA could regulate and doctors could prescribe.

Of course that’d put Stollman out of the fecal transplant business. He says that is fine with him.