Stool transplant

Also Known As: Stool transplant, Fecal microbiota transplantation, Fecal transplant

Fecal microbiota transplantation (FMT) also known as a stool transplant[1] is the process of transplantation of fecal bacteria from a healthy individual into a recipient.[2] It has been proven to be a highly effective treatment for patients suffering from Clostridium difficile infection (CDI), which produces effects ranging from diarrhea to pseudomembranous colitis.[3]Beginning in 2000, hypervirulent strains of C. difficile have emerged, which seem to be linked to antibiotics that are commonly used in empiric treatments.[4] In the U.S alone, an estimated 3 million new acute Clostridium difficile infections currently are diagnosed annually.[5] Of these, a subgroup will go on to develop fulminant CDI which results in approximately 300 deaths per day or almost 110,000 deaths per year.[6] Due to the epidemic in North America and Europe, FMT has gained increasing prominence, with some experts calling for it to become first-line therapy for CDI.[7]

Previous terms for the procedure include fecal bacteriotherapy, fecal transfusion, fecal transplant, stool transplant, fecal enema, and human probiotic infusion (HPI). Because the procedure involves the complete restoration of the entire fecal microbiota, not just a single agent or combination of agents, these terms have now been replaced by the new term 'Fecal Microbiota Transplantation'.[2] FMT involves restoration of the colonic flora by introducing healthy bacterial flora through infusion of stool, e.g. by enema, obtained from a healthy human donor.

Infusion of feces from healthy donors was demonstrated in a randomized, controlled trial to be highly effective in treating recurrent C. difficile, and more effective than vancomycin alone.[8][9] It also may be used to treat other conditions, including colitis,[10] constipation,[10] irritable bowel syndrome,[10] and some neurological conditions.[11][12]

The procedure involves single to multiple infusions (e.g. by enema) of bacterial fecal flora originating from a healthy donor. Most patients with CDI recover clinically and their CDI is eradicated after just one treatment.[2][13][14]While C. difficile is easily eradicated with a single FMT infusion, however, this generally appears to not be the case with ulcerative colitis. Published experience of ulcerative colitis treatment with FMT largely shows that multiple and recurrent infusions are required to achieve prolonged remission or 'cure'.[15] The procedure can be carried out via enema,[16] through the colonoscope,[17] or through a nasogastric or nasoduodenal tube.[18] Although a close relative is often the easiest donor to obtain and have tested, there is no reason to expect this to affect the success of the procedure as genetic similarities or differences do not appear to play a role;[2] indeed, in some situations a close relative may be an asymptomatic carrier of C.difficile, a disadvantage. Donors must be tested for a wide array of bacterial and parasitic infections.[2] The fecal transplant material is then prepared and administered in a clinical environment to ensure that precautions are taken.[19] The fecal microbiota infusions can be administered via various routes depending on suitability and ease, although enema infusion is perhaps the simplest. There does not appear to be any significant methodological difference in efficacy between the various routes. Repeat stool testing should be performed on patients to confirm eradication of CDI. In more than 370 published reports there has been no reported infection transmission.[20] A team of international gastroenterologists and infectious disease specialists have published formal standard practice guidelines for performing FMT which outline in detail the FMT procedure, including preparation of material, donor selection and screening, and FMT administration.[2] In 2012, a team of researchers at MIT founded OpenBiome, the first public stool bank in the U.S.[21] OpenBiome provides clinicians with frozen, ready-to-administer stool samples for use in treating C. difficile, and supports clinical research into the use of FMT for other indications.

A modified form of fecal bacteriotherapy (Autologous Restoration of Gastrointestinal Flora - ARGF) was being developed as of 2009.[22] Medical treatment with antibiotics often is the cause of C. difficile in a patient. An autologous fecal sample, provided by the patient before medical treatment, is stored in a refrigerator. Should the patient subsequently develop C. difficile, the sample is extracted with saline and filtered. The filtrate is freeze-dried and the resulting solid enclosed in enteric-coated capsules. Administration of the capsules is hypothesised to restore the patient's original colonic flora and combat C. difficile. However using one's own original colonic flora which made them susceptible to the CDI infection in the first place obviously holds a foreseeable disadvantage. As such, it is likely that following treatment the patient will still remain susceptible to CDI colonisation. In comparison, the introduction of donor flora facilitates colonisation with a more robust, CDI-resistant flora.

Researchers have also produced a standardised filtrate composed virtually entirely of viable fecal bacteria in a colourless, odourless form.[23] The preparation has been shown to be as effective at restoring missing and deficient bacterial constituents as crude homogenised FMT.[24]

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