Fecal microbiota transplant (FMT), also known as astool transplant,[2] is the process of transferring fecal bacteria and other microbes from a healthy individual into an unhealthy individual. FMT is an effective treatment forClostridioides difficile infection (CDI).[3][4][5] For recurrent CDI, FMT is more effective thanvancomycin alone, and may improve the outcome after the first index infection.[3][5][6]
Scanning electron micrograph ofClostridioides difficile bacteria from a stool sample
Fecal microbiota transplant is approximately 85–90% effective in people with CDI for whom antibiotics have not worked or in whom the disease recurs following antibiotics.[12][13] Most patients recover with a single FMT treatment.[8][14][15]
A 2009 study found that FMT was an effective and simple procedure that was more cost-effective than continued antibiotic administration and reduced the incidence ofantibiotic resistance.[16]
Once considered to be a "last-resort therapy" by some medical professionals, due to its unusual nature and invasiveness compared with antibiotics, perceived potential risk of infection transmission, and lack ofMedicare coverage for donor stool, position statements by specialists in infectious diseases and other societies[14] have moved toward acceptance as astandard therapy for relapsing CDI and toward US Medicare.[17]
It has been recommended thatendoscopic FMT be elevated tofirst-line treatment for people with deterioration and severe relapsingC. difficile infection.[8]
In November 2022, FMT (Biomictra) was approved for medical use in Australia,[1][18] andfecal microbiota, live (Rebyota) was approved for medical use in the United States.[19]
In May 1988, Australian professor Thomas Borody treated the firstulcerative colitis patient using FMT, which led to longstanding symptom resolution.[22] Following on from that, Justin D. Bennet published the first case report documenting reversal of Bennet's own colitis using FMT.[23] WhileC. difficile is easily eradicated with a single FMT infusion, 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.[22][24]
Clinical trials are underway as of 2020[update] to evaluate if FMT fromanti-PD-1 immunotherapy donors can promote a therapeutic response in immunotherapy-refractory patients.[25][26]
Once linked withnaturopathy,[27] there have been serious studies into treatingautism with fecal microbiota transplants. One such study was conducted inShanghai, China,[28] and an earlier study led byArizona State University.[29] The Arizona treatment has received a United States Patent (#11,202,808),[30] though the researchers stress the need for further research due to the small sample size and open-label nature of their research.[31]
A 2024 review found that fecal microbiota transplantation may reduce pain intensity and improve fatigue and quality of life in patients withfibromyalgia.[32][33][34] A 2023 review found that fecal microbiota transplantation improved symptoms ofirritable bowel syndrome compared to a placebo.[35]
A 2025 New Zealand study of 87 obese adolescents who were treated with fecal microbiota transplantation found that after four years there was an 11.2kg difference between the placebo group and the treated group. The treated group also had a waist circumference 8cm less than the placebo group and less body fat. Researchers at theLiggins Institute at Auckland University are working to develop a commercially viable treatment.[36]
Adverse effects were poorly understood as of 2016.[37] They have includedbacterial blood infections, fever,SIRS-like syndrome, exacerbation ofinflammatory bowel disease in people who also had that condition, and mild GI distress which generally resolve themselves soon after the procedure, including flatulence, diarrhea, irregular bowel movements, abdominal distension/bloating, abdominal pain/tenderness, constipation, cramping, and nausea.[37][38] There are also concerns that it may spreadCOVID-19.[39]
In 2019, a person died in the United States after receiving an FMT that contained drug-resistant bacteria, and another person who received the same transplant was also infected.[40][41] The USFood and Drug Administration (FDA) issued a warning against potentially life-threatening consequences of transplanting material from improperly screened donors.[40]
There are evidence-based consensus guidelines for the optimal administration of FMT. Such documents outline the FMT procedure, including preparation of material, donor selection and screening, and FMT administration.[11][14][42][43]
The gut microbiota comprises all microorganisms that reside along the gastrointestinal tract, including commensal, symbiotic and pathogenic organisms. FMT is the transfer of fecal material containing bacteria and natural antibacterials from a healthy individual into a diseased recipient.[14]
Preparing for the procedure requires careful selection and screening of the potential donor. Close relatives are often chosen on account of ease of screening;[14][42][44] however, in the case of treatment of activeC. diff., family members and intimate contacts may be more prone to be carriers themselves.[14] This screening involves medical history questionnaires, screening for various chronic medical diseases (e.g.irritable bowel diseases,Crohn's disease,gastrointestinal cancer, etc.),[42][45][46][47] and laboratory testing for pathogenic gastrointestinal infections (e.g.CMV,C. diff.,salmonella,Giardia, GI parasites, etc.).[14][42][46]
No laboratory standards have been agreed upon,[46] so recommendations vary for size of sample to be prepared, ranging from 30 to 100 grams (1.1 to 3.5 ounces) of fecal material for effective treatment.[13][42][44][47] Fresh stool is used to increase viability of bacteria within the stool[46][47] and samples are prepared within 6–8 hours.[42][46][47] The sample is then diluted with 2.5–5 times the volume of the sample with either normal saline,[42][46] sterile water,[42][46] or 4% milk.[14] Some locations mix the sample and the solvent with a mortar and pestle,[47] and others use a blender.[42][46][47] There is concern with blender use on account of the introduction of air which may decreaseefficacy[9] as well asaerosolization of the feces contaminating the preparation area.[42][47] The suspension is then strained through a filter and transferred to an administration container.[42][46][47] If the suspension is to be used later, it can be frozen after being diluted with 10%glycerol,[42][46][47] and used without loss of efficacy compared to the fresh sample.[42][44] The fecal transplant material is then prepared and administered in a clinical environment to ensure that precautions are taken.[9]
After being made into suspensions, the fecal material can be given throughnasogastric and nasoduodenal tubes, or through acolonoscope or as a retentionenema.[14]
One hypothesis behind fecal microbiota transplant rests on the concept of bacterial interference, i.e., using harmless bacteria to displacepathogenic organisms, such as by competitive niche exclusion.[48] In the case of CDI, theC. difficile pathogen is identifiable.[49] Recently, in a pilot study of five patients, sterile fecal filtrate was demonstrated to be of comparable efficacy to conventional FMT in the treatment of recurrent CDI.[50] The conclusion from this study was that soluble filtrate components (such asbacteriophages,metabolites, and/or bacterial components, such asenzymes) may be the key mediators of FMT's efficacy, rather than intact bacteria. It has now been demonstrated that theshort-chain fatty acidvalerate is restored in human fecal samples from CDI patients and a bioreactor model of recurrent CDI by FMT, but not by antibiotic cessation alone;[51] as such, this may be a key mediator of FMT's efficacy. Other studies have identified rapid-onset but well-maintained changes in the gutbacteriophage profile after successful FMT (with colonisation of the recipient with donor bacteriophages),[52][53] and this is therefore another key area of interest.
In contrast, in the case of other conditions such asulcerative colitis, no single culprit has yet been identified.[54] However, analysis of gut microbiome and metabolome changes after FMT as treatment for ulcerative colitis has identified some possible candidates of interest.[55]
The first use of donor feces as a therapeutic agent for food poisoning and diarrhea was recorded in theHandbook of Emergency Medicine by a Chinese man, Hong Ge, in the 4th century. Twelve hundred years later, Ming dynasty physicianLi Shizhen used "yellow soup" (aka "golden syrup") which contained fresh, dry or fermented stool to treat abdominal diseases.[56] "Yellow soup" was made of fecal matter and water, which was drunk by the person.[57]
The consumption of "fresh, warmcamel feces" has also been recommended byBedouins as a remedy for bacterialdysentery; its efficacy, probably attributable to the antimicrobialsubtilisin produced byBacillus subtilis, was anecdotally confirmed by German soldiers of theAfrika Korps duringWorld War II.[58] However, this story is likely a myth; independent research was not able to verify any of these claims.[59]
The first use of FMT in western medicine was published in 1958 by Ben Eiseman and colleagues, a team of surgeons from Colorado, who treated four critically ill people with fulminant pseudomembranous colitis (beforeC. difficile was the known cause) using fecal enemas, which resulted in a rapid return to health.[60] For over two decades, FMT has been provided as a treatment option at the Centre for Digestive Diseases inFive Dock, Australia, byThomas Borody, the modern-day proponent of FMT. In May 1988 their group treated the firstulcerative colitis patient using FMT, which resulted in complete resolution of all signs and symptoms long-term.[22] In 1989 they treated a total of 55 patients with constipation, diarrhea, abdominal pain, ulcerative colitis, andCrohn's disease with FMT. After FMT, 20 patients were considered "cured" and a further nine patients had a reduction in symptoms.[61] Stool transplants are considered about 90 percent effective in those with severe cases ofC. difficile colonization, in whom antibiotics have not worked.[12]
The firstrandomized controlled trial inC. difficile infection was published in January 2013.[3] The study was stopped early due to the effectiveness of FMT, with 81% of patients achieving cure after a single infusion and over 90% achieving a cure after a second infusion.
Since that time, various institutions have offered FMT as a therapeutic option for a variety of conditions.[22]
In July 2013, the FDA issued an enforcement policy ("guidance") regarding the IND requirement for using FMT to treatC. difficile infection unresponsive to standard therapies (78FR42965, July 18, 2013).[67]
In March 2014, the FDA issued a proposed update (called "draft guidance") that, when finalized, is intended to supersede the July 2013 enforcement policy for FMT to treatC. difficile infections unresponsive to standard therapies. It proposed an interim discretionary enforcement period, if 1) informed consent is used, mentioning investigational aspect and risks, 2) stool donor is known to either the person with the condition or physician, and 3) stool donor and stool are screened and tested under the direction of the physician (79FR10814, February 26, 2014).[68] Some doctors and people who want to use FMT have been worried that the proposal, if finalized, would shutter the handful of stool banks which have sprung up, using anonymous donors and ship to providers hundreds of miles away.[62][69][70]
As of 2015[update], FMT for recurrentC. difficile infections can be done without mandatory donor and stool screening, whereas FMT for other indications cannot be performed without an IND.[65]
The FDA has issued three safety alerts regarding the transmission of pathogens. The first safety alert, issued in June 2019, described the transmission of a multidrug resistant organism from a donor stool that resulted in the death of one person.[71] The second safety alert, issued in March 2020, was regarding FMT produced from improperly tested donor stools from a stool bank which resulted in several hospitalizations and two deaths.[72] A safety alert in late March 2020, was due to concerns of transmission ofCOVID-19 in donor stool.[73]
In November 2022, the AustralianTherapeutic Goods Administration approved faecal microbiota under the brand nameBiomictra,[1][18] and the US FDA approved a specificC. difficile fecal microbiota treatment under the brand nameRebyota,[19] administered rectally. In April 2023, the FDA approved a live spore capsule that can be taken by mouth, under the brand nameVowst.[20][74]
Across Europe, numerous stool banks have emerged to serve the increasing demand. While consensus exists,[42] standard operation procedures still differ. Institutions in the Netherlands have published their protocols for managing FMT,[47] and in Denmark institutions manages FMT according to the European Tissue and Cell directive.[46]
Previous terms for the procedure includefecal bacteriotherapy,fecal transfusion,fecal transplant,stool transplant,fecal enema, andhuman 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 been replaced by the termfecal microbiota transplantation.[14]
Cultured intestinal bacteria are being studied as an alternative to fecal microbiota transplant.[76] One example is the rectal bacteriotherapy (RBT), developed by Tvede and Helms, containing 12 individually cultured strains of anaerobic and aerobic bacteria originating from healthy human faeces.[77] Research has also been done to identify the most relevant microbes within fecal transplants, which could then be isolated and manufactured viaindustrial fermentation; such standardized products would be more scalable, would reduce the risk of infections from unwanted microbes, and would improve the scientific study of the approach, since the same substance would be administered each time.[78]
Elephants,hippos,koalas, andpandas are born with sterile intestines, and to digest vegetation need bacteria which they obtain by eating their mothers' feces, a practice termedcoprophagia. Other animals eat dung.[79]
Inveterinary medicine, fecal microbiota transplant is known as transfaunation and is used to treatruminating animals, like cows and sheep, by feedingrumen contents of a healthy animal to another individual of the same species in order to colonize its gastrointestinal tract with normal bacteria.[80]
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