Selection and Screening of Donor

The stool donor may be related or unrelated to the recipient. If related, the donor is typically a spouse or close relative. A systematic review by Gough and colleagues showed resolution of CDI in 93.3% of studies with related donors (n = 19 studies) and 84% of studies with unrelated donors (n = 4 studies). Kassam and colleagues similarly assessed the significance of donor type and found no difference in clinical outcome regardless if the donor was anonymous versus patient-selected. The investigators hypothesize that unrelated/anonymous donors likely harbor a completely different microbiome compared with related donors and thus may be more effective in “resetting” the microbiome of the recipients, although this has not been demonstrated in randomized studies. Furthermore, many patients prefer an anonymous donor to eliminate the sometimes awkward conversation requesting a stool sample from a family member.

With mild variation, donor screening protocols have been established to reduce the risks of transmission of an infection from the donor to recipient. Testing includes both stool and serum analysis as well as an extensive clinical and social risk assessment. A listing of donor assessment recommendations is included in Box 1 . The inclusion of such a screening protocol is important to prevent transmission of infectious organisms that may be harbored in donor stool. Additionally, we know little about the transmissibility of autoimmune diseases and other noninfectious conditions that may be influenced by changes in the microbiome. Although there have been instances of homeopathic or home-use of enemas to perform FMT without physician evaluation, this is strongly discouraged for the previously discussed reasons.

Some protocols will provide a laxative to the donor to assist with stool collection. We also recommend the donor avoid any foods (eg, nuts) to which the recipient has a known food allergy.

Regulations and Patient Consent

Currently, FMT is indicated for rCDI, although this application is still considered investigational. Despite Food and Drug Administration (FDA) oversight, physicians may perform FMT outside of a clinical trial (without an investigational new drug [IND] application and approval) for CDI that has not been responsive to standard antibiotic therapies; this has also been referred to as “enforcement discretion.” For non-rCDI applications, an IND must be submitted to the FDA.

From a clinical and research standpoint, any non-rCDI use of FMT is considered “off-label” and the evidence base of the benefits and risks should be strongly considered. In many cases, there are no data to justify its use. Following, we discuss the current evidence for CDI, inflammatory bowel disease (IBD), and other diseases in which FMT has been studied.

All patients should provide consent for FMT with the benefits, risks, process, and follow-up clearly explained to the patient. Some risks will be specific to the method of delivery. For example, with colonoscopy, we note the risk of reaction to anesthetic agents, discomfort during the procedure, gastrointestinal bleeding, and perforation. With regard to FMT, we also note the risk of transmission of an infectious agent or diseases/conditions for which the donor was not prescreened.

Screening of Recipient

There are no guidelines on screening requirements for FMT recipients. As noted previously, FMT is recommended for rCDI with less support for other disease indications currently. Although not standardized, we recommend baseline recipient testing for viral hepatitis, human immunodeficiency virus, and syphilis, because if the patient is diagnosed with one of these diseases post-FMT, further assessment can be performed to determine if the stool sample may have played a role.

Additional recipient screening considerations include comorbidities, such as immunocompromised status, which may increase the risk of adverse events.

Fecal Microbiota Transplantation Preparation and Administration

There is often some variation in FMT preparation across institutions where FMT is performed. The general process is the same, however, and involves mixing stool with a bacteriostatic liquid, removing particulate matter, and delivering donor stool to the patient. Patients should stop vancomycin (or any other antibiotic) at least 1 or 2 days before FMT administration.

Stool may be administered via several mechanisms, each with its own benefits and risks, as described in Table 1 . These include the following:

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  Oral (via nasogastric, nasoduodenal, or nasojejunal tube or capsule)

  
  
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  Colonoscopy (stool deposited into right colon or terminal ileum)

  
  
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  Enema

The process for performing FMT is described in Fig. 1 . Currently, there are 3 main methods of obtaining the donor sample:

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  Stool sample from unrelated or related local donor

  
  
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  Stool sample from a stool bank, generally shipped frozen on dry ice overnight

  
  
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  Frozen, encapsulated stool

Process of Fecal Microbiota Transplantation.

Stool is prescreened as described previously, either locally or at a stool bank before shipment. The latter provides a unique identifier that can be tracked back to the donor if necessary. Additionally, stool banks may retain a sample of donor stool for freezer storage for future studies or if the recipient develops a rare infection following FMT. For local donors, stool is obtained with the plan to transplant in less than 8 hours. Stool is mixed with normal saline (although mixing with milk has also been described) and vigorously shaken to ensure good mixing. Blenders (either supplied by the health care facility or brought in by the patient) have also been used, but will likely need to be discarded following stool preparation unless there is a method of disinfection. Mixed stool is passed through a filter or gauze to remove large particulate matter that may clog the colonoscope channel. Stool is then drawn up into 60-mL syringes (generally 4–5) and administered to the recipient. There are no guidelines for how much feces to deliver, although many agree that at least 50 g (or 250 mL diluent) should be adequate.

More recently, several stool banks have been formed. A stool bank collects stool from a set of prescreened donors, prepares and divides the donated stool, and freezes aliquots of screened stool that can then be shipped overnight to health care facilities. Samples are treated like a drug and frequently go through the institution’s pharmacy. This frozen sample is defrosted and drawn up into 60-mL syringes for administration. Alternatively, the stool bottle can be attached to the colonoscope’s water jet and sprayed into the colon rather than injecting syringes through the accessory channel. The use of a stool bank sample alleviates the need for mixing and filtering and is quite affordable (approximately $250 plus shipping). It also eliminates the need for the patient to ask a friend or relative to provide a stool sample. As that person would also need to be screened as described previously, a stool bank donor removes this step and associated cost.

Following FMT, we generally administer 1 dose of loperamide in the endoscopy recovery suite, although there are no clear data suggesting this alters outcomes. Some institutions will administer this medication before FMT. Additionally, we place the patient in reverse Trendelenburg for up to an hour with the goal of retaining stool in the colon as long as possible. At the time of discharge, we recommend home disinfection of all surfaces with a water-bleach cleaner (9:1 ratio) or sporicidal agent approved by the Environmental Protection Agency. We follow-up with the patient to assess for efficacy and adverse events.

There also has been the development of frozen, encapsulated stool. Capsules developed by OpenBiome (Medford, MA) use screened donor stool placed inside a size 0 capsule, which is then placed inside a size 00 capsule and frozen. Studies have been performed with trypan blue demonstrating an average of 115 minutes elapsing before the capsule opens; enough time to pass through the acidic environment of the stomach. The capsules are unique in the patented microbial emulsion matrix (MEM) technology using long-chain fatty acids as a carrier matrix to ensure delivery of live microbial communities. FMT capsules must be stored at −20°C or below and must be swallowed by the patient in less than 90 minutes from freezer removal.