After Antibiotics, the Feces Pill Remains

Some people with potentially lethal gut infections find that the only effective treatment is an orally-administered fecal transplant. The treatment is gaining acceptance among physicians.


NEW YORK — By the time patients arrive at the office of Bruce Hirsch, an infectious disease specialist at North Shore University Hospital in Long Island, they’re desperate. Many have diarrhea that strikes up to 20 times a day. They eagerly pay $1,200 out of pocket for the only thing that might make their lives normal again.

Hirsch offers them an orange pill, which they swallow. Underneath the pill’s outer shell are several smaller gel capsules. Inside the smallest capsule is a glycerin-suspended clump of bacteria that’s been extracted from human feces.

“It’s like a Russian doll,” Hirsch told me. “With a surprise in the middle.”

Hirsch is one of just a few dozen specialists in the country who perform fecal transplants—procedures used primarily to treat people who have severe gut infections caused by an overgrowth of a bacteria called Clostridium difficile.

But he’s also part of an even smaller group of practitioners who offer the transplants orally, with a pill regimen that was initially pioneered by Tom Louie, an infectious disease specialist in Calgary, Canada.

Hirsch’s interest in treating C. diff, as it’s sometimes called, was prompted by patients whose lives were completely destroyed—or ended—by their infections.

A few years ago, Hirsch saw a man in his 40s—an otherwise healthy runner who had developed a common respiratory infection. He was prescribed an antibiotic, and three days later he began experiencing severe diarrhea caused by a C. diff infection. Eventually he developed a complication of C. diff known as toxic megacolon, in which the colon swells and, in some patients, ruptures.

“Within 48 hours, he was on the table of an operating room having his colon removed,” Hirsch said. “He went from a healthy, jogging, middle-aged normal guy to an individual who is fated to shit out of his side for the rest of his life into a colostomy bag.”

More than 250,000 Americans each year require hospitalization for C. diff infections, and roughly 14,000 die from it, according to the CDC. In its recent report on drug resistance, the CDC classified C. diff as an “urgent” threat.

C. diff infections are often sparked when a person with an unrelated ailment takes a round of antibiotics, which kill off the gut’s “good” bacteria in the process. But Hirsch said he sees the bacteria even in patients who haven’t used antibiotics recently.

To him, this means C. diff is generating hearty, impossible-to-kill spores that allow it to jump from person to person, including within hospitals.

To make matters worse, certain strains of C. diff have evolved to withstand even the heaviest bombardment by drugs. Until recently, it could be treated with antibiotics, but in the late 1990s, the bug morphed and became much harder to eliminate.

“We knew we had a horrific problem,“ Mark Miller, former head of infectious diseases at the Jewish General Hospital in Montreal and a doctor who helped document C. diff’s transformation, told a Canadian news service. “We knew it was a bad C. diff, a more virulent C. diff.”

Increasingly, doctors are finding that their last remaining weapon is the bacteria from a healthy person’s bowels.


Fecal transplants aren’t a new therapy—the first was performed in 1958—but it’s still a relatively rare procedure because it’s logistically and, well, cognitively unappealing. Only about 20 doctors in the U.S. perform the procedure, and just 500 to 700 patients have received the transplants.

However, the rise of this more tenacious C. diff strain is pushing both patients and doctors to get over their fecal fears. In January, a study in the New England Journal of Medicine found that a far higher percentage of patients infected with C. diff recovered among a group being given an enema containing the stool of a healthy donor than did among those who were treated with antibiotics. Fecal transplants have been shown in that and other studies to cure 90 percent of C. diff infections within a few days.

But the procedure is far from simple. In clinics, they’re usually administered through a colonoscopy-type procedure, which is uncomfortable for sick and elderly patients, or through a tube stuck down the patient’s nose and into the stomach, which only exacerbates the patient’s natural feeling of disgust.

And because so few doctors offer them, some patients have been driven to try fecal transplants at home by themselves, usually by using a relative’s stool. But doing so outside a clinical setting, and without first testing the sample and donor for pathogens, is considered risky.

The first person Hirsch performed a fecal transplant on using the tube method was a 4’10 woman in her late 80s.

“She was very stoic, but it’s an awful experience,” he said.

By contrast, his “crapsules” are a breeze. “It’s a 10-capsule regimen with smiles and hugs from me. It’s a nothing procedure.”

Hirsch can’t meet the current demand for the pills, but with the help of a new biomedical startup, he’s hoping to get them in the hands of more and more patients.


Despite his years in medicine, Hirsch seems perpetually shocked by how poop—the archetypal odious substance—can be so curative. Shit’s inherent nastiness is, it seems, partly what’s been holding it back from curing countless C. diff patients by now.

“I mean, it’s really impressive how disgusting shit is,” he said. “Our experience of stool is this brief, six-inch flight time from rectum to water. But really, it’s not that it smells bad, it’s that the bad smell is deep. There’s a profundity. If you were describing a wine, it would be ‘woody notes, with a depth of pestilence underneath it.’”

At the same time, though, “Shit is a great drug.”

Antibiotics, on the other hand, are “like a blitzkrieg on the gut,” explained Gerard Honig, a neuroscientist and the director of operations at Symbiotic Health,  the startup working with Hirsch to take his poop pills to a broader market. Antibiotics usually kill what ails the patient, but they also sweep away much of the beneficial flora that keeps C. diff at bay. Meanwhile, C. diff hides out until the antibiotics have run their course, and then takes over the digestive system.

Clostridium difficile (Wikimedia commons)

It’s well known that the microbiome—the bacterial makeup—of each person varies, but that of healthy people appears to be able to successfully settle and grow in the gut of a sick person.

First, the transplanted fecal material joins the stream that courses through the intestines. Once in the colon, the bacteria divide and propagate.

“The C. diff gets crowded out,” Hirsch said. “It’s basically lost its ecologic niche.”

Within a few days, most of Hirsch’s patients have a normal bowel movement, sometimes for the first time in years.

Given how effective fecal transplants were, Hirsch knew he had to make them easier on the patients and his staff. After he heard that the Calgary doctor had made pills using donor feces, Hirsch ordered some empty capsules off the Internet, and, as an experiment, pipetted some Coca-Cola into them.

“I was really proud of myself, and I walked over to show some of my staff members,” he said, “But they were melting in my hand. They were falling apart.”

But his interest was piqued, and it wouldn’t take long for him to perfect the process.


These days, here’s how Hirsch’s pills go from rump to remedy:

First, they recruit the donors, who have so far largely consisted of family members of patients, other doctors, or generous-spirited regular Joes. To qualify, donors must be free of diseases such as HIV and hepatitis, and they must be able to—uh, donate—into a sterile plastic cup within a specific timeframe (that second part has turned out to be a surprisingly high bar.)

The poop is tested for yet another panel of pathogens, and if it’s clear, it gets sent on to the pill-making process.

First, a 50-gram lump of poop is put in a blender with a saline solution and pulsed until it’s homogenous.

“You basically get a shit shake,” Honig said.  “It contains bacteria, undigested fibers from your food, and the bacteria’s waste.”

The shake gets passed through filters of different sizes that remove the larger pieces. What remains gets poured into a tube and nested inside a white, printer-sized centrifuge.

The gravitational pull causes the material inside to separate into three layers: On the bottom, a dense pellet the consists of undigested fiber, and on top, a liquid consisting of saline and the waste products of the fecal bacteria. In the middle lies what Hirsch and Honig are after: A dense, light-brown paste, about the consistency of smooth peanut butter, made up of the fecal bacteria itself.

“At that point, it’s not offensive,” Honig said. “When you get rid of the waste products of the bacteria, it doesn’t smell as bad.”

Still, for good measure, the bacterial layer gets covered up by multiple layers of gelatin capsules. The final one is golden-hued and has a light citrus taste.

“So when they swallow shit,” Hirsch said, “all they get is a sense of the orchids of Florida in the back of their mouth."

Some patients are curious about the origins of their specific poop pills, much as one might be for a sperm or egg donor.

“One of my patients was very happy to know that the donor was a brilliant, PhD scientist,” he said. “He was vastly relieved to know that his donor was very accomplished.”


Desks at the Harlem Biospace. (Olga Khazan)

Despite how sought-after they are, fecal transplants have hit repeated regulatory and payment hurdles. Earlier this year, the Food and Drug Administration briefly began requiring doctors to submit investigational new drug applications if they wanted to perform fecal transplants, but the agency backed down several months later when physician and patient advocacy groups said the process was too cumbersome for a potentially life-saving procedure.

For now, Hirsch is only obligated to inform patients that fecal transplants are an experimental procedure, that there are risks of infection associated with it, and that there are risks he’s not aware of that might come up in the future.

Many doctors, Hirsch included, say they must charge patients out-of-pocket because the procedure costs them thousands of dollars in man-hours and materials but only nets a small reimbursement from Medicare and most other insurers, since the poop-pill procedure is not considered a full colonoscopy.

“By making it easier on the patient, we’re financially penalized,” he said. “It’s a shitty way of doing business, no pun intended.”

That could be changing, though, since the Affordable Care Act will eventually tie Medicare reimbursement rates for hospitals partly to their infection-based readmission statistics, which would create an incentive to cure C. diff patients as promptly and efficiently as possible.

Hirsch says he still gets more calls than patients he can see. In an effort to improve the pill-making process, as well as to find a way to get the pills distributed more widely, Hirsch has partnered with Honig at Symbiotic Health.

The startup is based out of Harlem Biospace, a new biotech incubator in Manhattan. Decked in reclaimed-wood furniture and the latest gadgetry, it aims to bring the cheap, nimble tech startup philosophy to medicine.

“Right now we’re applying for grants, talking to investors, and looking for hospitals who want to develop a competitive edge, starting with the North Shore Long Island Jewish System,” Honig said. “We want to take this capsule therapy, which we know works, we want to make it of higher quality and higher purity.”

Honig sees his company eventually consulting for other doctors who want to try the pill method, or even helping push out production to distribution centers around the country.

“Me with a blender and pipette is not that different from the way drugs are made,” he said. “But all the drugs you take are made by guys with blenders and pipettes working at a much larger scale.”

Eventually, Honig and Hirsch think they might be able to use gut microbes to predict which patients are likely to contract C. diff infections after taking antibiotics. Or, even further in the future, they might be able to select for, say, a vegan or gluten-free donor based on the symptoms of the individual patient.

“Maybe we would find some Buddhist monastery somewhere where they have the perfect diet,” Hirsch said. “Maybe we would have this holy shit line. We don’t really know right now though.”