When you hear about transplants, it is easy to imagine an exchange of organs such as the heart or lungs between individuals. In some cases, organ transplants occur one at a time. In other cases, multi-organ transplantation is needed — although, the number of organs involved typically does not exceed single digits. But what about transplantation which depends on transferring trillions of parts at a given time? Clearly, this could not be a single or even multi-organ transplant but rather the transplant of an “organ” that is inherently multifaceted: the gut microbiome.
Fecal Microbiota Transplantation
Fecal microbiota transplantation (FMT) is a therapeutic method that consists of transferring gut bacteria from a healthy individual to an individual in need of improved gastrointestinal health. Patients can directly receive FMTs from healthy donors through a colonoscopy, enema, or swallowing a capsule containing freeze-dried feces that are laden with intestinal microflora.
Who May Need a Fecal Transplant?
Currently, FMT is used to largely treat patients with recurrent Clostridioides difficile infection (CDI) or to manage ulcerative colitis, a form of inflammatory bowel disease. In both cases of disease, the gut microbiome is imbalanced (also known as dysbiosis) in such a way that there are adverse consequences for the host. In CDI, the opportunistic pathogen C. difficile has colonized the gut and secretes toxins that make the host sick. Furthermore, C. difficile can readily survive antibiotic treatment by achieving a state of dormancy called “spore formation”. In contrast, the disease state of ulcerative colitis is not based on a specific bacterium but is instead believed to be linked to alterations in microflora diversity. For example, ulcerative colitis patients have been observed to have population changes amounting to decreases in Bacteroides and Enterococcus; and increases in Escherichia and Shigella.
Microbiome Transplants - How Does It Help?
FMT restores the balance of the gut microbiome in many ways. In the case of CDI treatment, the infusion of nearly an immeasurable number of bacteria can lead to C. difficile being outcompeted in the intestinal environment. Similarly, for ulcerative colitis, the influx of so many new bacteria restore microbial diversity to one akin to a healthier gut. However, it is not only the bacteria that drive healing but also everything else that may be found in the intestinal milieu (e.g., bile acids and metabolites). For example, in a mouse model, microbial production of the short-chain fatty acid valerate was restored after FMT and was noted to be a driving cause in inhibiting C. difficile growth. Recent work has also shown that FMTs can have a positive effect on cancer treatments. In these small trials, melanoma patients initially resistant to immunotherapy became responsive after receiving FMTs from cancer patients who were cured using that specific form of immunotherapy. These proof-of-principle studies highlight the gut microbiome’s influence on health and potentially open avenues in pairing FMT with therapeutics for other diseases as well.
However, like all medicine, treatment with FMT also bears some level of risk for side effects. Some known risks include the potential transmission of pathogenic bacteria as well as cells or molecules which can lead to a predisposition for other diseases. Despite the long history of using FMT as a therapy, it was not until November 2022 that the U.S. Food and Drug Administration officially approved the first FMT-based therapeutic for recurrent CDI (Rebyota). This seeming delay is because there are several regulatory hurdles associated with giving a treatment that is an innate biological mixture of many different things with no single ingredient that provides the cure. That said, FMT is still endorsed by medical organizations as an alternative form of treatment if deemed necessary. As such, rigorous screening of donor stool samples is performed to strongly limit the risks that may befall the recipient patient.
Fecal microbiota transplantation has incredible potential as a form of medicine. With the first approval of Rebyota™ by the U.S. FDA, there is now regulatory precedence for approving similar gastrointestinal agents in the future. This sets the stage for the potential availability of more FMT products that may be useful in helping treat other chronic illnesses.
Types of Fecal Microbiota Transplantation (FMT) Procedures
Fecal microbiota transplantation (FMT) is most commonly conducted through colonoscopy. In this procedure, a gastroenterologist inserts a colonoscope along the entire length of the colon. As the scope is slowly withdrawn, a solution containing screened donor stool is introduced into the colon to restore healthy gut microbiota.
In certain cases, FMT may be administered using a nasogastric or nasoduodenal tube, which is inserted through the nose and extends into the duodenum, the section of the small intestine connected to the stomach. While this approach does not require bowel preparation, it carries an increased risk of complications such as aspiration pneumonia.
Additional methods of FMT delivery include oral capsules and rectal enemas, offering alternative options based on patient preferences and medical conditions.
Fecal Transplant Donor
FMT donors can be sourced from an established stool bank where individuals undergo comprehensive screening, or patients may opt to choose a donor personally.
A suitable fecal transplant donor should be a healthy adult who:
- Has not used antibiotics within the last six months
- Has a fully functioning immune system
- Is free from infectious diseases
- Does not have a history of chronic gastrointestinal conditions, such as inflammatory bowel disease
Donors undergo thorough medical screening to rule out potential infections and conditions, which typically include tests for:
- Hepatitis A, B, and C
- HIV
- Syphilis
- Intestinal parasites (e.g., Giardia, worms)
- Clostridioides difficile (C. difficile)
- Any additional conditions as deemed necessary by the physician
Healthcare providers will inform both donors and recipients about the necessary tests and precautions before proceeding with the transplant.
Preparing for Fecal Microbiota Transplantation
Patients should inform their healthcare provider about all current medications, including prescription drugs, over-the-counter supplements, and any allergies. Preparation for the procedure may involve discontinuing antibiotic use at least 48 hours beforehand, following specific dietary guidelines such as a clear liquid diet if undergoing colonoscopic FMT, and completing bowel preparation, which may include the use of laxatives or enemas. For procedures requiring sedation, such as colonoscopy or endoscopy, it is essential to arrange for someone to accompany the patient and provide transportation post-procedure.
What to Expect During a Fecal Transplant Procedure
The procedural steps vary based on the chosen delivery method:
- Colonoscopy: The donor stool is processed into a liquid suspension mixed with a saline solution. Patients are positioned on their side, sedated, and the colonoscope is carefully advanced through the colon. As the scope is withdrawn, the stool solution is dispersed along the colon lining.
- Endoscopic or Nasogastric Administration: A flexible tube is inserted either through the nose or mouth to deliver the stool solution into the small intestine.
- Capsules or Enemas: The transplant material is encapsulated or introduced rectally, typically requiring less invasive preparation.
Following the procedure, patients may be advised to take medications that slow bowel movements to help retain the transplanted microbiota in the colon for optimal effectiveness.
Post-Procedure Recovery and Potential Side Effects
FMT is generally safe and well-tolerated, even among patients with recurrent C. difficile infections and in pediatric populations. The recovery period usually involves mild and temporary side effects, which depend on the method of delivery. Patients may experience bloating, gas, and abdominal cramping, often due to air introduced during the procedure. Constipation can occur as a result of prescribed anti-diarrheal medications, and minor leakage of the transplant solution from the rectum is also possible. Although serious complications are rare, they can include the transmission of undetected infections if donor screening is inadequate, aspiration pneumonia when FMT is delivered via a nasogastric or nasoduodenal tube, and complications related to colonoscopy or endoscopy, such as bleeding, infection, or intestinal perforation. Patients should adhere to post-procedure care instructions and promptly report any persistent or severe symptoms to their healthcare provider.