Dr. Google is Full of Sh**
By Kate Wheeling
BU News Service
You can’t unread this. It’s a step-by-step guide to self-administered fecal transplants for patients with Inflammatory Bowel Diseases (IBD). Mix wheat or oats with water and salt in a cheap blender—I’d buy one special for the occasion. Collect human feces from a healthy donor and add it to the mix. Draw the fecal-oat smoothie into a turkey baster, hop in the bath tub, and release it into your intestines via the shortest route (hint: it’s the rectum). Lie down immediately and employ any acrobatics necessary to hold in the solution for as long as possible.
The internet is brimming with miracle cures for incurable diseases, and fecal microbiota transplants like these are among the latest. Optimistic patients willing to overlook the lack of clinical trial results for the experimental treatment forego conventional care. They find their own donors, add saline and stir—then deliver the mixture to the intestines in at-home enemas. Fecal transplants boast impressive stats for the treatment of antibiotic resistant infections—cure rates hover between 90 and 95%—which explains why anyone would consider going through the ordeal described above.“It just freaking worked,” said an anonymous self-experimenter in an online Irritable Bowel Disease forum, who developed the protocol described above. “I’m fixed.”
Interest in fecal transplants has exploded within the last few years. In 2009, there were two scientific publications on fecal microbiota transplants. In 2013, that number rose to 77. Thanks to the Internet, interest outside the scientific community has increased in parallel. “This is the age we live in,” says Dr. Michael Surette, Professor of Medicine at McMaster University. “The internet is such a mixed blessing when it comes to information.” Healthy individuals are put off by ‘the ick factor,’ but for patients with Inflammatory Bowel Disease that’s a non-issue. They’re looking for alternatives to standard therapies which are never curative, often ineffective, and can sometimes produce symptoms that are worse than those of the disease itself. But not everyone is convinced that these transplants are the right alternative.
The truth is, fecal transplants are over-hyped. They may have near perfect success rates for bacterial infections, but they don’t work nearly as well for Inflammatory Bowel Disease. Half a dozen small trials have looked at the transplants for IBD patients so far and success rates ranged widely – anywhere from 90% down to 0%.
Fecal transplants are exactly what they sound like—the transfer of diluted fecal material into a patient’s gastrointestinal track, The procedure has been trending on the internet for the last five years but it predates the World Wide Web by more than a millennium. The first reference to fecal transplants came in China’s 4th century handbook for emergent medicine, “Handy Therapy for Emergencies.” There, Ge Hong described the use of human fecal ingestion by mouth to treat food poisoning and diarrhea.
Since then, application strategies have advanced. Today we use plastic tubes, enemas, and colonoscopies to deliver the treatment. The aesthetic concerns have virtually disappeared, but the safety concerns have yet to be addressed.
The first clinical trial involving fecal transplants concluded just over a year ago, and it was hailed an unequivocal success. The study, published in the New England Journal of Medicine, followed three groups of patients with recurrent Clostridium difficile infections—a nasty bacterial infection often unaffected by standard antibiotic treatments. One group of 17 patients received fecal transplants, the remaining 13 patients received standard courses of antibiotics. The transplants worked so much better, the trial ended early. Almost immediately leading gastroenterologists and fecal transplant pioneers called for the treatment to become the standard procedure, and not just for C. diff infections, but for a grab bag of gut disorders.
Proponents claimed that the only thing preventing doctors from accepting the new treatment was “the yuck factor.” In reality, doctor’s reservations were always, and still are, about more than our innate aversion to feces.
“My concern is not about efficacy,” said Wael El-Matary, head of Pediatric Gastroenterology at the University of Manitoba. “My concern is about safety.”
There are glaring risks associated with transferring feces between individuals, especially when immunocompromised patients with Inflammatory Bowel Disease are involved. Chief among them: infection. “Just because someone is healthy, does not mean they are not carrying pathogens,” says Surette. In healthy individuals, dangerous pathogens are kept in check by healthy bacteria, but they won’t behave nearly as well inside immunocompromised Inflammatory Bowel Disease patients. The carriage rates of gut pathogens in the general population are largely unknown, but Surette says they’re not insignificant. Many patients who choose to self-treat with fecal transplants don’t screen their donors at all. “You’re really rolling the dice when you try and do this without knowing,” he says.
Known pathogens are only the beginning.“We can screen for those that we know about,” says El-Matary, “but there are millions and millions of microbes that we don’t know about.” We’ve seen the consequences of this before; in the 70s and 80s thousands of hemophiliacs were infected with HIV via contaminated blood products, before the virus was identified.
The results of fecal transplants can be unpredictable. Transplanting microbes is an immune shock. The foreign microbes could quiet the immune system, or they could send it into overdrive. When the immune system overreacts in the intestines, you can get what doctors call “leaky gut.” Basically, bacterial products seep out from the gut into the body, which is bad news for even the healthiest of individuals.
There is also a low, but real risk of physical damage to the rectum or colon, especially when patients are administering transplants themselves. This is a particular danger in patients with Inflammatory Bowel Disease, whose tissues are already inflamed and fragile.The long term safety risks are completely unknown.
The uncertainty surrounding fecal transplants stems from a lack of data. Only two dozen doctors in the US perform the procedure. There are less than 500 transplants reported in the literature according to Surette, but the number of self-administered transplants is likely higher. Online IBD communities and forums are clogged with testimonials about the procedure, but no one is really keeping track. “The problem with the internet is that adverse affects, treatment failures and infections are not being reported,” says Surette. “There’s a false sense of success out there.”
There are 18 clinical trials underway in North America looking at fecal transplants as a treatment for Inflammatory Bowel Disease. There may not be much data on the adverse affects yet, but as the number of patients in these trials grows those risks may become reality.
The FDA is doing its best to mitigate these risks by regulating fecal transplants as a drug. This means that until fecal solutions and the protocols for their administration are standardized, doctors will have to submit an Investigational New Drug application every time they perform the procedure. Standardization is still a long way off. “In most studies, each patient has a different donor, so it’s hard to find a microbial signature of success (or failure),” says Surette. There is no definition of a ‘normal, healthy microbiota.’ At this point the only thing that can be said of our intestinal bacteria with any certainty is that they affect the host’s physiology. How and why that happens is still being worked out.
A recent editorial in Nature argues that the FDA shouldn’t look at fecal transplants like a drug at all, but as a tissue. After all, the transplanted material is not a single active compound that acts on a known pathway to treat a symptom or disease, like many drugs; it’s a collection of hundreds of active compounds—a living biological material. It may be impossible to standardize the dynamic, living populations. According to the authors, regulating fecal transplants as a tissue could spur research and get the procedure to patients as quickly as possible, before they turn to underground donor sources (i.e. their friends and families—and even pets according to the Nature editorial).
But less stringent regulations could actually drive more patients to self-administer the procedure. William, a Crohn’s patient who requested his last name be withheld, made fecal transplant pills himself from a stool donation from his sister—a donor he trusted enough not to screen. William didn’t bother to tell his doctor about his self-experiment either. “Why put that stress on someone about the risks they believe I’m taking, when I feel confident that I’m taking a decent amount of precautions?” he explained in an email. If patients believe it’s only a matter of time before the FDA drops those regulatory hurdles it creates an illusion of safety.
The hype around fecal transplants is not unfounded, given the high success rates of the low-tech treatment. It even fits in with the current trend in the US towards the use of “natural” treatments over standard procedures. But the economic and health risks associated with self-administered fecal transplants are not inconsequential. Patients who use transplants might put off treatments that could potentially keep them in remission and thus invite unforeseen health outcomes like infection or flares. Even if the treatment works for Inflammatory Bowel Disease—and the data to back up those claims is still a year or two away—it may never be safe enough to become a procedure that takes place in your doctor’s office, much less at home.