Dr. Arnab Ray is a gastroenterologist at the Ochsner Clinic in New Orleans, Louisiana, USA. He has performed over 20 Fecal Microbiota Transplantations (FMT) to treat Clostridium difficile and is currently enrolling patients in the Rebiotix Punch CD clinical trial. He is also starting a clinical trial for FMT using Ulcerative Colitis.
Fecal microbiota transplantation (aka stool transplant, fecal transplant) has been getting a lot of attention in the media recently. Patients have many questions, and physicians do not always have the answers. Just to give a little background to the conversation, fecal transplants have been around in various forms since the 4th century as documented in Chinese writings of Ge Hong. They reappeared in Western medical literature most notably in 1958, when Eiseman successfully treated 4 patients with what was likely Clostridium difficile (C. diff) colitis (the infection was not named until the 1980’s). It disappeared again until C. diff started becoming more common, more virulent, and more resistant to standard antibiotics regimens at the turn of the century. Physicians rediscovered this treatment and began using it, but concerns about safety soon arose and the FDA became involved. Earlier this summer, the FDA released a statement requiring a research protocol in place in order to use FMT for the purposes of tracking adverse events. After an inundation of research applications, they reversed their position and simply requested that physicians follow minimal standards of safety when performing a FMT.
In this article I discuss FMT for the treatment of C. diff infection. The reason that we are restricting this discussion just to C. diff is that FMT is currently only FDA approved for treatment of C. diff infection, and it is still considered an experimental therapy. That means that doctors are not supposed to use it as a treatment for other diseases unless they are doing so within the supervision of an approved research trial. In order for the FDA to approve a treatment for a disease, it must be proven both safe and effective. We have a good number of studies showing this to be the case for C. diff, but not as many for other diseases. As a result, your doctor is technically not legally allowed to use FMT to treat other diseases, and can get into trouble for doing so, especially if something goes wrong.
That being said, there are a large number of clinical studies currently underway across the country to investigate the use of FMT in other gastrointestinal diseases. For example, our department is interested in studying the effectiveness of FMT in patients with mild to moderate Ulcerative Colitis. If you are interested in being a participant in one of these trials, please see here. Finally, if you are interested in performing FMT on yourself for a condition other than C. diff, you may run into different reactions from your doctor. It is reasonable to ask him to test your donor for safety purposes, but keep in mind that insurance companies are under no obligation to pay for such testing, and your doctor will be hard pressed to help you if your condition worsens.
Once you have been diagnosed with C. diff diarrhea, your doctor will likely treat you with an antibiotic such as Metronidazole (flagyl), Vancomycin, Fidaxomicin (dificid), or Xifaxan (rifaximin). When these antibiotics do not work, a fecal transplant is typically considered. Often, it is the patient who will raise this, as they are looking for anything to give them their life as they knew it back. Many patients who are wary of the side effects and overuse of antibiotics ask for fecal transplant as an alternative to antibiotics. As the use of fecal transplant in modern medicine is still considered experimental, a lot of questions typically arise between acknowledging this as a treatment option and actually receiving it.
Which doctor do I ask?
Although this seems like a simple question, the answer can actually be quite complicated. Physicians typically try to stick with treatments within their field of expertise, and C. diff qualifies as both an infectious disease and a disease of the gastrointestinal tract. As a result, both infectious disease (ID) specialists and gastroenterologists (GI’s) tend to get consulted for this disease. Sometimes a colorectal surgeon will be consulted if the colitis is so severe that the colon needs to be removed to save the patient’s life, but they typically do not continue management of the disease beyond the surgery. In my experience, I have seen both infectious disease doctors and gastroenterologists perform fecal transplants.
Infectious disease doctors typically will administer the fecal transplant via an enema or a nasogastric tube (a temporary tube from the nose down to the stomach), and gastroenterologists have the additional ability to administer the transplant via colonoscopy or upper endoscopy (a lighted camera guided into the stomach and small intestine). I personally prefer the colonoscopy approach as I can see what the colon looks like, and make sure there is not another reason that the patient is sick, such as inflammatory bowel disease (Crohn’s disease and Ulcerative Colitis). I also think that patients have an easier time retaining the fecal transplant material when it is administered 6 feet into their colon, as opposed to an enema which is just infused in the bottom portion of the colon, but both approaches have proven effective.
As far as which doctor to ask, it simply depends on the personal experience of the doctors in your town. This is typically not handled by primary care providers or family practitioners, but I would not be surprised if some have tried to take this on. Many doctors simply refer patients who need a fecal transplant to a larger university hospital or tertiary care referral center where physicians are more familiar with the required testing and have experience with performing the procedure.
How do I talk to my doctor about fecal transplant?
With medical advances changing from day to day, it can be hard for a doctor to keep up with all the new treatments, especially the treatments which are not officially FDA approved and still considered experimental, such as fecal transplant. The best way to get your doctor’s attention is to show them the evidence. Every doctor in the world has heard of the New England Journal of Medicine. If your doctor has not, then I suggest you find a new one. A landmark article came out in January 2013 which tested fecal transplant versus vancomycin treatment and concluded: “The infusion of donor feces was significantly more effective for the treatment of recurrent C. difficile infection than the use of vancomycin.” Physicians nowadays are taught to practice evidence based medicine, and this is about as good evidence as you can provide. Once your doctor agrees that you need a fecal transplant for your C diff infection, you need to find a GI or ID doctor who can perform one.
Here is a list to get you started in case your doctor does not know who to call:
Where do I find a donor?
Some doctors may be hesitant to perform fecal transplants because finding a donor takes a lot of work, and no one knows what makes a perfect donor. There is some consensus as to which tests to run at a minimum to screen the donor, but locating a donor and having them available for your appointment to discuss fecal transplant goes a long way towards making the process smoother. A donor can be anyone who is generally in good health, has not had antibiotics in the last 3-6 months, has not had a cancer of the gastrointestinal tract, has not traveled to an area where diarrhea is endemic, and does not have constipation or diarrhea. A doctor experienced in FMT will perform a more thorough questionnaire and testing of the donor’s stool and blood to make sure that they are suitable. Most people typically use a spouse, family member, or close friend. As a doctor, I am always glad when a patient brings their donor to their appointment so that I can take a good history face to face and explain the testing to everyone (all confidentially of course).
Within the last few months, some companies such as Open Biome and the Taymount Clinic in England are making screened stool commercially available, so there are options available if you cannot find a suitable donor, or are too shy to ask!
There is understandably a lot of frustration from patients who are seeking fecal transplant when they talk to their doctors, because many doctors do not perform this procedure. Here are some reasons that your doctor may give for being hesitant to move forward with a fecal transplant.
Is it safe?
Primun non nocere. One of the first things a doctor is taught in medical school is “first, do no harm”. Can we guarantee that fecal transplants are not harmful? Right now, we think fecal transplants are safe, but we just don’t know for sure. The only way to know this is to follow a large number of patients in standardized research protocols and patient registries over a number of years. A large number of studies are currently underway with FDA supervision to try to answer this question. So far in the medical literature, there have been no documented cases of transmitting infection by fecal transplant, but it will almost inevitably happen at some point. It is important to realize that there are thousands of bacteria and viruses in the colon that we do not even know how to grow in culture, so we cannot routinely test for all of them. Bacteria which may be completely happy and content in one person’s colon may cause havoc and disease in another colon, especially someone who is already sick. We are learning that everyone’s gut microbiota is unique, just like their fingerprint.
What are the long term effects?
Again, we don’t know the answer to this question. There have been studies following patients from a few months to a few years, but there are only case reports beyond that. There have been reports of patients gaining weight after their fecal transplant because they have taken on some of the metabolic characteristics of their donor. The truth is, we are just beginning to understand the interaction of our gut bacteria with our bodies. Until we have a better grasp on the long term implications of manipulating gut bacteria, a lot of practitioners feel like we are playing with fire. Medical history is filled with examples of medications and vaccines being brought out with good intentions before they were fully understood, but with lethal consequences. Just look no further than the history of the polio vaccine, or more recently the use of an adenovirus vector for gene therapy at the University of Pittsburgh. We may find out in 10 years that people who undergo fecal transplants develop colon cancer at greatly increased rates due to the manipulation of the gut microbiota that we do not currently fully understand. Although unlikely, If that happens, then the only ones who benefit will be the lawyers.
How do I do it?
If you are a doctor who takes care of patients 60 to 80 hours a week and then spends your “extra” time fighting insurance companies, there really is not much time to learn how to do a new experimental procedure, especially if there are other doctors who are willing to do it. Fecal transplant is not something that they teach everyone in medical school or residency, and there is no standardized or “right way” to do it, which makes it even more difficult to learn how to do. On top of that uncertainty, all it takes is one case to go wrong to bring on a lawsuit. Unfortunately, that is the reality of practicing medicine in our litigation happy society. It is extremely difficult to defend yourself against a bad outcome when the rules of the game are so unclear, and for a lot of doctors who have gone into considerable debt to train and then spent their lives building their practice, an experimental procedure with so many unknowns is simply not worth the risk, so they pass it on to someone else. The good news is that more and more doctors are becoming familiar and willing to perform this procedure to help battle the epidemic of C. diff.
The good news is that FMT is gaining more widespread acceptance, and the doctors who are performing this effectively are getting their names out. I treat patients from across the state and the entire Gulf South region. There is also no hotter topic of interest than the human microbiome among gastroenterologists. You could not attend a single discussion at the recent American College of Gastroenterology conference without FMT coming up. I anticipate that as more cost effectiveness studies emerge and treatment protocols become standardized and more feasible to the average practitioner, FMT will eventually replace antibiotics as first line treatment for C. diff.
As the volume of research done on the human microbiome increases, we will get further clarity on the use of FMT for other gastrointestinal diseases such as ulcerative colitis, Crohn’s disease, and irritable bowel syndrome. We will even begin to see its potential application in non gastrointestinal diseases such as depression, obesity, and autoimmune disorders. Keep in mind that research does take time and patience to perform. Not every study comes back positive and unforeseen complications arise. There is limited funding for this sort of research because there is very little incentive for a pharmaceutical company to develop something as readily available as stool! The big trick will be to standardize stool and mass produce it in pill form. In the meantime, keep the lines of communication open with your doctor so that you can continue to have a mutually respectful and honest discussion.
If you enjoyed this article, you might also enjoy How to talk to your doctor about fecal transplant: a patient’s perspective
American Journal of Gastroenterology Lecture: Intestinal Microbiota and the Role of Fecal Microbiota Transplant (FMT) in Treatment of C. difficile Infection. Lawrence J. Brandt , MD. Am J Gastroenterol 2013; 108:177–185.
Guidelines for Diagnosis, Treatment, and Prevention of Clostridium difficile Infections. Christina M. Surawicz , MD 1 , Lawrence J. Brandt , MD2 , David G. Binion , MD3 , Ashwin N. Ananthakrishnan , MD, MPH4 , Scott R. Curry , MD5 , Peter H. Gilligan , PhD 6 , Lynne V. McFarland , PhD7 , 8 , Mark Mellow , MD9 and Brian S. Zuckerbraun , MD 10. Am J Gastroenterol 2013; 108:478–498.
Duodenal Infusion of Donor Feces for Recurrent Clostridium difficile. Els van Nood, M.D., Anne Vrieze, M.D., Max Nieuwdorp, M.D., Ph.D., Susana Fuentes, Ph.D., Erwin G. Zoetendal, Ph.D., Willem M. de Vos, Ph.D., Caroline E. Visser, M.D., Ph.D., Ed J. Kuijper, M.D., Ph.D., Joep F.W.M. Bartelsman, M.D., Jan G.P. Tijssen, Ph.D., Peter Speelman, M.D., Ph.D., Marcel G.W. Dijkgraaf, Ph.D., and Josbert J. Keller, M.D., Ph.D. N Engl J Med 2013;368:407-15.