Fecal microbiota transplantation (FMT) is a medical procedure that transfers the community of gut bacteria from a healthy donor into the digestive tract of a patient to help treat or prevent illness. FMT is most commonly used to resolve recurrent C. difficile infections but has also been used in clinical trials to treat a wide range of illnesses including autoimmune and metabolic disorders, neuropsychiatric conditions, and cancer. Researchers are working to fully understand how FMT works but the procedure can generally be seen as a transplant that restores a functioning microbiome (or community of bacteria) in a patient. This community of bacteria helps the body function by performing a variety of tasks such as digesting food, training the immune system, and modulating brain function.

There is no standard way that FMT treatments are manufactured, but most stool banks (including OpenBiome and the University of Minnesota Microbiota Therapeutics Program) follow the general steps outlined below.

1. Donor screening and stool donation: A donor who has passed screening for potential health risks provides a stool sample.
2. Processing: The stool sample is mixed with a buffer to help bacteria survive being frozen. The resulting mixture is filtered to remove fiber and solid particles that may clog the machinery used to administer the FMT treatment.
3. Storage and Administration: Newly made FMT treatments are stored frozen in a -80 degree Celsius freezer. Treatments are shipped overnight on dry ice to hospitals where they are once again stored in freezers or thawed and administered to a patient.

The FDA regulates FMT as an investigational drug. This means that patients may only access FMT through a clinical trial. The exception to that rule is patients with recurrent C. difficile infections that have not responded to standard antibiotic regimens. Through a compassionate use policy known as enforcement discretion, these patients may receive an FMT from their physician if they have provided informed consent.

More information can be found in OpenBiome’s white paper titled “Regulatory Oversight for Fecal Microbiota Transplantation”

FMT treatments may be administered in three modalities

1. Upper Delivery (though a nasoenteric/gastric tube or EGD)
2. Lower Delivery (though colonoscopy, sigmoidoscopy, or enema)
3. Orally (through a capsule form)

The most suitable modality for a patient depends on their medical unique history and health status. FMT is typically an outpatient procedure, and patients are usually able to return home a few hours after the procedure.

Overall, the cure rate of FMT from clinical trials and real-world settings suggests that FMT treats about 80% of antibiotic-resistant C. difficile infections. In OpenBiome’s experience, colonoscopic delivery is the most effective modality followed by lower delivery and capsules.

More information can be found in OpenBiome’s white paper titled “Efficacy of Fecal Microbiota Transplantation.”

Because FMT is classified as an investigational drug by the FDA, no claims can be made about the procedure’s safety. However, FMT is now standard of care for recurrent C. difficile infections and is recommended by the Infectious Disease Society of America, American College of Gastroenterology, and the British Gastroenterological Society for patients who have failed antibiotic therapy.

Based on data collected from thousands of patients treated in clinical trials as well as real-world settings through OpenBiome, the potential therapeutic benefit of FMT outweighs the safety risks for most patients with recurrent C. difficile infections. However, each patient has a unique medical record and health status that may affect this risk/benefit assessment. It is important that patients have a conversation with their physician to determine whether FMT is a suitable treatment option for them. Patient populations that require special consideration include immunocompromised patients, patients with fulminant C. difficile, and pediatric patients.

More information can be found in OpenBiome’s white paper titled “Current Evidence on the Safety of Fecal Microbiota Transplantation (FMT) for C. difficile infection.”

Patients receiving an FMT are at risk of the following

Infection: Most stool banks (including OpenBiome and the University of Minnesota Microbiota Therapeutics Program) screen for common pathogens and antibiotic-resistant bacteria. However, we cannot completely eliminate the risk of known and unknown infectious organisms contained in donor stool that could be spread to patients. Transmission of infectious disease could lead to post-FMT infections including diarrhea, sepsis, and fatal adverse events.

Allergy and Anaphylaxis: Although there have been no reported cases of allergy or anaphylaxis, we recommend that patients be screened for food allergies before receiving an FMT. If patients have a severe food allergy or anaphylaxis, they should consider using FMT treatment made from a donor who has abstained from the offending allergen.

Non-communicable diseases: The microbiome is associated with many aspects of the human body including metabolism, neurologic function, the immune system, and cancer. Therefore, there is a theoretical risk that patients may develop a disease that is related to their donor’s gut microbiota. Stool banks (including OpenBiome and the University of Minnesota Microbiota Therapeutics Program) typically exclude potential donors who have conditions that may be related to the microbiome but the risk of acquiring these conditions and other unknown microbiome-mediated disease cannot be completely eliminated.

Long-Term Risks: There is relatively little data on the long-term safety outcomes of FMT. Only a few studies have followed up with patients beyond 6 months post-FMT. Although these studies show no or little long-term health consequences associated with FMT, the long-term safety profile of FMT remains unknown.

More information can be found in OpenBiome’s white paper titled “Current Evidence on the Safety of Fecal Microbiota Transplantation (FMT) for C. difficile infection.”