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Poop Transplants And Microbiome Makeovers: How We’ll Engineer Our Bacteria To Feel Better

Don’t get squeamish. You’re going to take a poop pill one day soon, and it’s going to change your life.

Poop Transplants And Microbiome Makeovers: How We’ll Engineer Our Bacteria To Feel Better

Irritable bowel syndrome is one of those amorphous diseases of our modern times. Its potential causes involve the double whammy of diet and stress, and it’s hard to diagnose except by its symptoms, which can include bloating, abdominal pain, and diarrhea or constipation. More than 1 in 10 people in the U.S. suffer from it.

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Unsurprisingly, there’s a thriving market for treatments that may or may not help. “Anti-diarrheals, anti-depressants, there’s several herbal supplements. Behavioral therapy. The list goes on and on,” says Olga Aroniadis, a researcher and internist at Montefiore Medical Center in New York. “Many of these patients are miserable. Their quality of life is terrible, and new therapies are needed.”

Aroniadis, like a number of researchers who study diseases of the gut, is now looking to a fresh idea that shows much promise–what she calls the ultimate probiotic: human feces.

Scientists are just starting to explore the mysteries of the trillions of microorganisms that inhabit our gut. Some diseases in which the gut’s “microbiome” may play a role are more obvious, like Crohn’s disease or irritable bowel syndrome. But this massive community inside our digestive tract is also thought to influence other more complicated metabolic conditions that are huge public health problems like obesity and diabetes, as well as seemingly unrelated diseases. For example, microbiome research is even a new frontier for understanding autism, as autistic kids have been shown to have abnormal or less diverse intestinal bacteria. There is a well-documented “gut-brain connection,” in the form of what’s called the enteric nervous system, which controls your digestive system but also is deeply linked with your brain–and thus your mood. Researchers are starting to show that this connection means that what’s happening in our guts may be affecting our behavior in ways we can barely even fathom.

Most research work on the gut microbiome done so far has been descriptive, not therapeutic. Scientists are studying how microbial communities differ among the healthy and the sick, which is the first step to understanding whether or how these organisms help maintain our well-being or contribute to illness. For example, one NYU researcher, Martin Blaser, has been documenting the linkage between the overuse of antibiotics–which wipe out our healthy microbiomes–and the rise of childhood obesity. But it’s still not clear whether obesity is really the result of an “unhealthy” microbiome or even what an unhealthy microbiome looks like.

“We are just learning about a very powerful collection of organisms in our body,” says Aroniadis, “and we’re just at the beginning stages of understanding the way they influences health and disease.”

While there are few concrete answers yet, some doctors are now looking to more active microbial interventions. Fecal matter transplants (or FMTs) are procedures that date back decades and possibly even centuries, but have been mostly on the fringe of medical science. Basically, through an enema or colonoscopy or nasal gastric tube, you transfer a slurry of stool and saline solution from a healthy person–and the healthy ecosystem of microbes in the poop–into the intestines of a sick person. It’s much safer if a doctor does it, but the process itself is relatively simple: Patients have done it at home using no more than a blender, a bag and funnel, lubricant, and some other accessible supplies.

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It’s enough to make even doctors squeamish, but bear with us. The idea has gotten a lot of attention in the last few years because it works. It’s been almost a miracle cure for patients suffering from an emerging superbug called Clostridium difficile or C. diff, an infection that colonizes the gut after some people take antibiotics and is often resistant to antibiotic treatment itself. In severe cases, it can cause stomach pain, fever, and watery diarrhea 10 to 15 times a day. Half a million people in the U.S. get it every year, and 15,000 people die from it. Yet, of the last few years, data has shown that about 90% of patients with serious, recurring C. diff infections who aren’t helped by antibiotics have been cured by a fecal transplant.

In recent years, as word spread on the Internet of the success of FMT for treating C. diff, suffering patients began begging doctors to perform the procedure. But FMTs were an avant garde treatment in ambiguous territory with the FDA, and few doctors would do it. That left many resorting to finding poop donors in family members or friends and using DIY methods. Finally, in 2013, the FDA relented. It announced a “compassionate” exemption that basically said it would look the other way for doctors who wanted to help C. diff patients without applying for a paperwork heavy, time intensive investigational new drug application. But still, this is an exception: fecal matter transplants haven’t yet gone through clinical trial approval as a biological drug–as the FDA views feces material–for any illness, including C. diff.

Around the same time, Mark Smith, a microbiologist from MIT whose friend was had resorted to a DIY transplant to treat his C. diff infection, decided to launch what essentially has become an Amazon for poop. OpenBiome became a nonprofit stool bank that could distribute standardized, safe fecal samples in vials and provide support for doctors who wanted to use them. Only about 3% of interested donors end up passing OpenBiome’s stringent health screening tests, and once they do, they are paid $40 a poop pop (real “regulars” can earn as much as $13,000 a year, in theory, just from their poop).

Ever since, OpenBiome has been shipping more and more vials to doctors and researchers around the world. Today, it’s sent out more than 5,000 vials of human fecal material to healthcare partners in nearly all U.S. states and six countries. And business keeps picking up: June marked a record number 740 shipments.

When I talk to Smith, he seems relieved that I don’t want to talk about how he is paying people for their poop (that story’s been done, and done, and done.) I wanted to talk about where the poop was going. Because OpenBiome isn’t just sending raw material for C. diff patients: For investigators who have applied for and received the FDA’s approval, it’s also assisting in a growing number of clinical trials for many other kinds of diseases. A U.S. government database of current clinical trials around the world lists 82 results for “fecal matter transplant” related to conditions as diverse as liver disease, metabolic syndrome and obesity, HIV, Crohn’s disease, pancreatitis, and Type 2 diabetes.

“I think there’s a lot of hype in this space. A lot of people look at the success that we have had for C. difficile, and think it will work 90% of the time for more complicated conditions. But if even a fraction of the hype is true–and I think it probably will be–then that’s going to have a huge impact,” says Smith.

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Montefiore’s Aroniadis is one of the researchers in the middle of a clinical trial, using OpenBiome’s material. In 2012 and 2013, she collaborated on research that showed a fecal transplant helped a small number of irritable bowel syndrome patients feel major relief even 11 months after one transplant, done by an endoscopy. Overall, the patients reported 70% improvement. Now, she is recruiting patients for a larger, randomized clinical trial that will more formally test patients who receive an FMT against those who get a placebo. Importantly, OpenBiome has recently developed a capsule that patients in the trial will swallow, rather than require a more invasive procedure. Pills both make it much easier to receive a transplant more regularly and could allow release at different points in the digestive tract for more pinpoint delivery of necessary microbes.

“We’ll be looking to see what happens to the microbiome before and after the fecal transplant–if they are at a baseline and if that changes. If they do have a microbial disturbance, can we fix that and if we fix that, do their symptoms mirror the change?,” she says. “If it does work, the benefit would be extremely far-reaching.”

George Russell, a researcher at Boston Children’s Hospital, has embarked on similar clinical trials using FMT to treat ulcerative colitis, a type of inflammatory bowel disease. He says it “would be an amazing advance” if doctors could avoid today’s treatments, which usually involve suppressing the immune system and come with major risks. Already, he knows that most IBD patients have a far smaller range of microbial species in their guts, compared to healthy people Stool transfers help restore that diversity and all the possibly beneficial chemical compounds that those microbes release into our bodies.

Today, we are in the crude early days of microbiome engineering. Most researchers agree that the FDA is right to regulate fecal transplants carefully for now. There have been no long-term studies on the effects of giving someone a microbiome makeover–it’s possible there may be unintended ones. “It’s not completely different than transferring another organ, like a liver or a kidney. It’s not completely understood. It’s possible that your gut microbiome gives a predisposition to other diseases,” says Russell.

One day, when our knowledge advances, however, we may all take our own individualized microbiome pills–probably put together in a lab rather than from human donors. Smith, of OpenBiome, sees a future where people will get a microbiome “refresh” after taking antibiotics or getting sick. Other studies show how we may look to our microbiomes to influence broad aspects of our health. Blaser’s NYU lab, for example, has shown that mice implanted with the gut microbiome from a thin person grow thin and those implanted with the microbiome of an obese person grow obese.

“You could say to a person, you have these bacteria now and we know that if we can change a few of them, you’d feel much better. Being able to individualize and personalize the therapeutic effect of a fecal transplant–that’s the next step,” says Aroniadis.

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That may be in the future, but it’s a future that’s advancing very fast.

About the author

Jessica Leber is a staff editor and writer for Fast Company's Co.Exist. Previously, she was a business reporter for MIT’s Technology Review and an environmental reporter at ClimateWire.

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