The body contains a dense population of microorganisms in the lower intestine, or colon. These microbes form an important part of your digestive system that can help to digest certain foods. They also participate in various other parts of human physiology and contribute to regulation of metabolism and instruction of the immune system. The microorganisms that normally reside in the colon are highly specialized and organized into a community. The term microbiota refers to the entire communities of these microorganisms, which are engrafted into the recipient intestines during the procedure.
The only medical condition that can currently be treated outside clinical research trials is Clostridium difficile (C. difficile) infection that fails standard therapies. However, there is great interest in trying IMT for other indications. Our program is participating in a trial for autism, for example, which is being conducted at the Arizona State University. We are also working to develop IMT protocols for inflammatory bowel disease and metabolic syndrome, which we anticipate will begin once we secure federal and local regulatory approval and secure sufficient resources. At this time we offer IMT only for qualifying patients with C. difficile infection. It is important to emphasize that refractory C. difficile infection is characterized by major suppression of normal microbial communities in the gut, which differs from most other situations where the microbial communities may be altered in composition, but not diminished.
There are very simple, fast, and accurate stool tests that are used to diagnosed this infection. People are most vulnerable to catching C. difficile infection during or after treatment with antibiotics. Normal microbial communities in the gut are able to keep C. difficile in check, but antibiotics suppress the normal microbes creating a state vulnerable to infection. Intestinal microbial communities may not return to a normal state for up to several months after taking antibiotics. An individual can become infected if he or she comes into contact with C. difficile spores, which germinate in the intestine, giving rise to vegetative forms of bacteria that produce toxins. It is the toxins that make people sick. The usual symptoms are diarrhea. However, sometimes people can become extremely ill with high fever and their colon may stop working altogether. The standard treatment for C. difficile infection is more antibiotics. C. difficile is resistant to most antibiotics, but there are some that can suppress it, including metronidazole (Flagyl), vancomycin (Vancocin), rifaximin (Xifaxan), and fidaxomicin (Dificid). However, even these antibiotics cannot get rid of all the C. difficile spores, and their administration can perpetuate the infection because they also continue to inhibit the normal microbes. Therefore, the infection can come back once the anti-C. difficile antibiotics are stopped. Patients commonly develop a cyclical pattern of infection – treatment – recurrent infection. Every recurrence increases the chances of failure of antibiotic therapy, and some patients can develop multiply recurrent C. difficile infection syndrome.
During this procedure normal microbial communities are introduced into the colon, and reestablish its normal microbial composition. There are a number of theories that may explain how normal microbes keep C. difficile in check. This is an area of active research and we are keenly interested in this question.
We do not put in stool into patients! We implant microbial communities or microbiota. In our program we separate the microbial fraction from the fecal material of healthy donors in the laboratory. These microbes, which are mostly bacteria, are held in a freezer with a preservative in a frozen suspension. The material cannot be released for clinical use until all up-to-date testing is completed on the donor and the material itself. Each person’s fecal microbiota are made up of hundreds of different microbial species, and the composition is somewhat different in each person. However, there are more similarities than differences. In patients with recurrent C. difficile infection syndrome, very few normal bacteria are left. When a new microbial community is introduced, it quickly takes up residence and reconstructs the damaged microbial gut ecology. The vast majority of IMT procedures in our program are done via a colonoscopy. We have the most experience with this route of administration, which also allows a diagnostic examination of the colon. Some patients may qualify for an oral form of IMT during which they swallow encapsulated preparations of microbiota. Regardless of route of administration, the patients need to remain on an antibiotic to suppress C. difficile until 2 days prior to the procedure. Keeping C. difficile suppressed with antibiotics gives the new bacteria the best chance of succeeding.
It is important to minimize chances of transmitting an infection with this procedure. Therefore, the donor is screened for various infectious diseases. These include HIV, hepatitis, and various intestinal infections. Recent science also tells us that gut microbes may play important roles in the body’s metabolism and immune function. Therefore, we exclude donors with metabolic problems like obesity and diabetes, as well as any immune diseases or problems. We exclude donors with any gastrointestinal complaints and people who take any prescription medications. The donors also cannot have antibiotics for at least 6 months before donation.
The overall success rate in the literature is about 90%. A randomized trial was reported from the Netherlands in January of 2013 in the New England Journal of Medicine reporting > 80% success rate. That trial was stopped early because the antibiotic group was doing much worse. Since the program’s inception in 2008, our center has experienced a 90% success rate with one infusion attempt (> 220 patients, years 2008-2014). Patients who fail cure with one attempt can receive another FMT, which brings the success rate to 98%.
The procedure appears to be very safe, although the data are limited to large case series and only one small, randomized trial. Patients with underlying inflammatory bowel disease can experience a transient flare of colitis, although in the long run they generally do better after ridding themselves of C. difficile infection. Since the transplant material is derived from feces, proper donor screening and testing is essential. Our donors go through many steps to be qualified. They complete a large questionnaire, which includes a section similar to one done at the blood banks, but in addition the questions screen for metabolic, gastrointestinal, immunologic, and neurologic disorders. The donors undergo a full history and physical examination, and are tested for various systemic infections, including HIV, hepatitis, syphilis, as well as metabolic and autoimmune problems. The stool is tested for various enteric infections, including C. difficile. However, it is important to emphasize that some risks remain unknown since we may not know all the pathogenic organisms that exist. Some microbes may be able to cause problems only in certain individuals, e.g., people with a weak immune system. So far, limited evidence collected from a number of centers suggests this risk is very small.
The only known indication for which IMT is known to work is recurrent or recalcitrant C. difficile infection. It is appropriate to consider this procedure if the chance of recurrence remains very high despite antibiotic treatments. Typically, that means two or more recurrences after stopping anti-C. difficile antibiotics. Additional risk factors include advanced age, inflammatory bowel disease, history of severe C. difficile infection with hospitalization, and recent use of additional antibiotics for indications other than C. difficile infection. It should be noted that if patients require frequent antibiotics for other indications, e.g., bladder infections, the beneficial effects of the fecal transplant may be very short-lived
Currently it is not known if this procedure can help any other condition. While there is a great deal of interest in additional indications, IMT for non-C. difficile indications has to be done within clinical research trials. You can see if you qualify for any such trials at ClinicalTrials.gov.
There are some insurance companies that do cover a small part of the cost. In our program we do not charge recipients for material preparation done in our donor program. The material is typically implanted via a colonoscopy, which also has a diagnostic objective, and the procedure is usually covered. Nevertheless, nuances may exist depending on your specific insurance and situation.
We need to learn a great deal about this procedure and the role microbes play in our health. Therefore, it is likely that you will be invited to participate in some of our research projects. Studies generally involve collection of fecal specimens. If you are interested, we will discuss your potential participation. Importantly, your care will not be influenced by the decision to participate in these studies or not, although clinical outcome data will be collected in the course of your treatment.