DESCRIPTION / INFORMATION

The human intestine contains a complex community of bacteria, viruses, fungi, and other microorganisms known collectively as the gut microbiome. Illness, antibiotics, and other factors can disrupt this community. Fecal microbiota transplantation (FMT) attempts to restore a healthier microbial ecosystem by transferring processed stool from a carefully screened donor into a patient’s intestinal tract.

FMT has become an important treatment option for selected patients with recurrent Clostridioides difficile infection, commonly called C. difficile or C. diff. At the same time, FMT is being studied for many other diseases, sometimes with far less evidence. In addition, the United States now has FDA-approved microbiota products derived from human stool, making it important to distinguish conventional FMT from standardized microbiota-based therapies.

These 20 questions explain what FMT is, how it works, when it is used, what the evidence shows, how donors are screened, what risks remain, how FDA regulates the field, and how FMT differs from newer microbiome therapies.

At a Glance: FMT and Related Microbiota Therapies

Conventional FMTREBYOTA®VOWST®Typical Probiotic
What is it?Processed donor stool containing a complex microbial communityStandardized donor-derived fecal microbiota productPurified donor-derived fecal microbiota spore productOne or several selected microorganisms
FDA-approved?NoYesYesProduct-dependent; ordinary supplements are not approved to treat recurrent C. diff
Current U.S. roleUsed under an IND or, in limited circumstances, FDA enforcement discretionPrevention of recurrent C. diff after antibacterial treatment in adultsPrevention of recurrent C. diff after antibacterial treatment in adultsNot an equivalent substitute for FMT or approved microbiota therapy
How given?Colonoscopy, enema, capsules, or upper-GI delivery, depending on protocolRectallyOrally as capsulesUsually orally
Contains an entire stool-derived community?Broad, complex donor microbiotaBroad donor-derived microbiotaEnriched bacterial sporesMuch narrower selection of organisms
Main established indicationRecurrent C. diff in selected patientsPrevention of recurrent C. diffPrevention of recurrent C. diffVaries; not established as replacement therapy for recurrent C. diff

REBYOTA was approved by FDA in November 2022 and VOWST in April 2023. Both are indicated for prevention of recurrent C. difficile infection in adults after antibacterial treatment for recurrent disease. Conventional FMT itself remains an unapproved biological product under FDA regulation. (U.S. Food and Drug Administration, 2022a, 2023a, 2023b)

QUESTIONS

1. What is fecal microbiota transplantation (FMT)?

Fecal microbiota transplantation is the transfer of processed stool from a carefully selected donor into the gastrointestinal tract of another person.

The purpose is not simply to transfer “good bacteria.” Stool contains a complex community of bacteria, bacteriophages and other viruses, fungi, microbial products, metabolites, and other biological material. FMT transfers a microbial ecosystem, not just one or two organisms.

The best-established use of FMT is treatment of selected patients with recurrent Clostridioides difficile infection after standard antibiotic therapy has failed to prevent repeated episodes.

The term fecal microbiota transplantation is preferable to informal terms such as “fecal transplant” or “stool transplant” in scientific and medical writing, although those expressions are sometimes used when explaining the procedure to patients.

2. How does FMT work?

The exact mechanism is not completely understood.

Antibiotics and illness can greatly disturb the normal gut microbial community. In C. difficile infection, this disruption can reduce what is sometimes called colonization resistance:  the ability of the normal microbiome to prevent potentially harmful organisms from taking over.

FMT introduces a diverse microbial community that can help restore ecological functions in the intestine. Proposed mechanisms include:

  • competing with C. difficile for nutrients and space;
  • restoring microbial diversity;
  • changing bile-acid metabolism;
  • producing substances that inhibit C. difficile;
  • restoring metabolic functions of the microbiome; and
  • influencing immune and intestinal-barrier function.

It is therefore more accurate to think of FMT as an attempt to restore an intestinal ecosystem rather than simply adding “healthy bacteria.”

3. What conditions is FMT used to treat?

The clearest clinical role is recurrent C. difficile infection.

The American Gastroenterological Association’s 2024 guideline suggests fecal microbiota-based therapy for most immunocompetent adults with recurrent C. difficile infection after completion of standard antibiotic therapy. It also supports conventional FMT in selected patients hospitalized with severe or fulminant C. difficile infection that is not responding to antimicrobial treatment. (Peery et al., 2024)

Researchers have investigated FMT for many other conditions, including:

  • ulcerative colitis;
  • Crohn’s disease;
  • irritable bowel syndrome;
  • metabolic disorders;
  • liver disease;
  • autism-related symptoms;
  • some neurologic disorders; and
  • other illnesses in which the microbiome may play a role.

However, evidence of microbiome involvement in a disease does not automatically mean that FMT is an effective treatment.

AGA currently recommends against conventional FMT for ulcerative colitis, Crohn’s disease, pouchitis, and irritable bowel syndrome outside clinical trials.

4. What is the scientific evidence for FMT’s effectiveness?

Evidence is strongest for recurrent C. difficile infection.

Multiple randomized trials and systematic reviews have shown that fecal microbiota-based treatments can substantially reduce recurrence in appropriately selected patients.

However, it is better not to state that FMT simply “works in 80-90% of patients.” Success rates vary according to:

  • how recurrent disease is defined;
  • whether one or multiple treatments are given;
  • route of administration;
  • donor preparation;
  • antibiotic regimen;
  • patient population;
  • length of follow-up; and
  • whether conventional FMT or an FDA-approved microbiota product is being studied.

Current AGA guidance therefore focuses more appropriately on whether evidence supports treatment in a particular clinical situation rather than assigning one universal success percentage. (Peery et al., 2024)

For disorders other than recurrent C. difficile infection, results are much more variable and generally remain investigational.

5. How is conventional FMT administered?

Conventional FMT can be delivered in several ways.

Methods have included:

  • colonoscopy, in which prepared microbiota material is delivered into the colon;
  • enema or other rectal administration;
  • oral capsules containing processed donor material; and
  • upper gastrointestinal delivery through a nasogastric, nasoduodenal, or similar tube.

Each method has advantages and disadvantages.

Colonoscopy allows direct delivery into the colon but requires bowel preparation and carries the usual risks of colonoscopy and sedation.

Capsules avoid an invasive procedure but must be manufactured so that the material can survive transit through the upper gastrointestinal tract.

Upper-GI delivery has been used historically but introduces considerations such as aspiration risk.

The method chosen depends on the clinical situation, product, institution, patient characteristics, and current treatment protocols.

Importantly, FDA-approved microbiota products have their own specific administration methods: REBYOTA is administered rectally, while VOWST is taken orally.

6. Is FMT safe?

FMT can be relatively safe when appropriately used with carefully screened donor material, but describing it simply as “safe” understates an important fact: it transfers living biological material from one human being to another.

Most adverse effects are mild and temporary. However, serious infections have occurred.

FDA has documented transmission of pathogenic organisms through FMT, including multidrug-resistant bacteria. In one reported episode, two immunocompromised recipients developed invasive infections with an ESBL-producing strain of Escherichia coli, and one patient died. FDA subsequently strengthened donor-screening and testing requirements.

Additional infections linked to donor stool containing enteropathogenic or Shiga-toxin-producing E. coli prompted further FDA safety actions.

FMT should therefore be considered an effective therapy with real but manageable risks, not a harmless transfer of “good bacteria.”

7. What are the main risks and side effects of FMT?

Short-term effects may include:

  • abdominal discomfort or cramping;
  • bloating;
  • gas;
  • diarrhea;
  • constipation;
  • nausea; and
  • occasionally fever.

There are also risks related to the method of administration. Colonoscopy, for example, carries risks of bleeding, perforation, sedation complications, and other procedural adverse events.

A more important concern is the possibility of transmitting an infectious organism that was not recognized in the donor.

Known concerns have included:

  • multidrug-resistant organisms;
  • pathogenic E. coli;
  • other bacteria;
  • parasites;
  • viruses; and
  • potentially newly emerging infectious agents.

FDA added SARS-CoV-2 screening and testing precautions after evidence showed that infected people can shed the virus in stool.

There is also theoretical concern about transferring microbiome characteristics associated with chronic diseases. Whether FMT can transmit long-term susceptibility to metabolic, immune, neurologic, or other conditions remains an area of study.

8. How are stool donors screened and selected?

Donor screening is much more extensive than simply asking whether someone feels healthy.

Potential donors undergo detailed medical and behavioral screening for factors that could increase the risk of transmitting disease. Depending on the protocol, this may include questions concerning:

  • recent illness;
  • antibiotic exposure;
  • gastrointestinal disease;
  • infectious exposures;
  • travel;
  • hospitalization;
  • health-care exposure;
  • medications;
  • metabolic and immune disorders; and
  • other health conditions.

Blood and stool are tested for specified infectious agents.

FDA has specifically required additional safeguards concerning multidrug-resistant organisms, including screening for risk factors and laboratory testing. These concerns arose after documented transmission of an ESBL-producing E. coli strain through investigational FMT.

Screening requirements have also evolved in response to newly recognized pathogens such as SARS-CoV-2.

No screening system can reduce risk to zero. This is one reason donor screening must continue to evolve as new infectious threats are recognized.

9. Who should not receive FMT, or who requires special caution?

There is no single universal list because risk depends on the patient’s condition, reason for treatment, method of administration, and type of microbiota therapy.

Immune status is particularly important.

AGA’s 2024 guideline suggests conventional FMT for mildly or moderately immunocompromised adults with recurrent C. difficile infection after standard antibiotic treatment, although the certainty of evidence is very low.

For severely immunocompromised adults, however, AGA suggests against fecal microbiota-based therapies because potential harms may outweigh uncertain benefits.

Other concerns may include:

  • medical instability;
  • conditions making colonoscopy unsafe when that route is planned;
  • severe bowel pathology or perforation risk;
  • inability to tolerate the planned method of administration; or
  • other conditions that increase infectious or procedural risk.

The decision should therefore be individualized rather than based on a simple checklist.

10. Is FMT approved by the U.S. Food and Drug Administration?

This question requires an important distinction.

Conventional FMT itself is not FDA-approved.

FDA generally considers FMT a biological product and drug for which an Investigational New Drug application, or IND, would ordinarily be required.

However, FDA currently exercises enforcement discretion under limited circumstances for conventional FMT used to treat C. difficile infection that is not responding to standard therapies. This means FDA does not intend to enforce the IND requirement in those specified circumstances when the conditions in its guidance (including informed consent and appropriate donor screening) are satisfied. (U.S. Food and Drug Administration, 2022a)

At the same time, FDA has approved two donor-derived microbiota products:

REBYOTA® (fecal microbiota, live-jslm) was approved in 2022 for prevention of recurrent C. difficile infection in adults after antibacterial treatment for recurrent CDI.

VOWST® (fecal microbiota spores, live-brpk) was approved in 2023 for the same general indication and was the first orally administered fecal microbiota product approved by FDA.

Thus, saying simply that “FMT is investigational” is no longer an adequate description of the U.S. regulatory landscape.

11. Can FMT be done at home or with do-it-yourself methods?

It should not be.

DIY FMT bypasses the extensive donor screening, laboratory testing, manufacturing controls, clinical assessment, and monitoring used to reduce the risks of medically administered treatment.

A donor may appear completely healthy while carrying:

  • drug-resistant bacteria;
  • pathogenic intestinal organisms;
  • viruses;
  • parasites; or
  • other microorganisms capable of causing serious disease in a recipient.

The transmission of multidrug-resistant E. coli documented by FDA illustrates why apparent donor health is not sufficient protection.

There is also no reliable way for a person preparing stool at home to standardize dose, processing, storage, or administration.

FMT should therefore be performed through qualified medical care or an appropriately supervised clinical trial.

12. How long do the benefits of FMT last, and is repeat treatment sometimes needed?

Successful microbiota therapy for recurrent C. difficile infection can provide durable protection, but recurrence can still occur.

Some patients respond after one treatment, while others require additional therapy.

Long-term outcome depends on many factors, including:

  • the patient’s underlying health;
  • number and severity of previous C. difficile episodes;
  • subsequent exposure to antibiotics;
  • future hospitalization or health-care exposure;
  • age;
  • immune status; and
  • other recurrence risk factors.

FMT should therefore not be thought of as permanently “installing” a new microbiome that can never again be disturbed.

13. What preparation is required before and after FMT?

Preparation depends on the treatment being used.

Patients with recurrent C. difficile infection generally first receive appropriate antibacterial treatment for the active infection. Fecal microbiota-based therapy is then used after completion of that treatment to help prevent recurrence. This sequence is reflected both in current clinical guidelines and in the approved indications for REBYOTA and VOWST.

Conventional colonoscopic FMT may also require bowel preparation similar to that used for colonoscopy.

Specific products have their own instructions concerning the timing of antibiotics, bowel preparation, diet, fasting, or other medications.

After treatment, patients should be told which symptoms are expected and which require medical attention. Follow-up is important for determining whether C. difficile recurs and for identifying adverse events.

Patients should follow the particular instructions for the treatment they receive rather than relying on a generic FMT preparation protocol.

14. Where can patients access FMT, and is it covered by insurance?

FMT and microbiota-based therapies may be available through gastroenterology practices, academic medical centers, hospitals, specialized infectious-disease programs, and clinical trials.

Availability depends on whether a center provides:

  • conventional FMT;
  • an FDA-approved microbiota product;
  • both; or
  • investigational microbiome treatment through a research study.

Insurance coverage varies considerably.

Coverage may depend on:

  • the diagnosis;
  • number of C. difficile recurrences;
  • prior treatments;
  • medical-necessity criteria;
  • product selected;
  • procedure used;
  • provider network; and
  • individual insurance policy.

Because conventional FMT, REBYOTA, and VOWST have different regulatory and reimbursement pathways, patients should verify coverage for the specific therapy being proposed, rather than asking only whether their plan “covers FMT.”

15. How does FMT compare with probiotics, prebiotics, and defined microbiota products?

These treatments are not interchangeable.

Probiotics generally contain one or a limited number of microorganisms intended to provide a health benefit.

Prebiotics are substances used by microorganisms in ways that may benefit the host. Many dietary fibers can function as prebiotics, although not every fiber is a prebiotic.

Conventional FMT transfers a highly complex donor-derived microbial community together with other stool components.

Standardized fecal microbiota products, such as REBYOTA and VOWST, are manufactured under controlled conditions and have undergone FDA review for defined indications.

Researchers are also developing defined microbial consortia:  carefully selected combinations of specific organisms intended to reproduce some of the beneficial ecological effects of FMT without transferring whole donor stool.

The field is therefore moving from relatively heterogeneous donor-stool preparations toward increasingly characterized and standardized microbiota therapeutics.

16. What is the difference between conventional FMT and FDA-approved microbiota products?

They share the general goal of restoring resistance to recurrent C. difficile infection, but they are not the same thing.

Conventional FMT is prepared from donor stool according to a clinical or stool-bank protocol. The microbial content varies naturally from donor to donor and donation to donation. Conventional FMT has not itself been approved by FDA.

REBYOTA is an FDA-approved, donor-derived fecal microbiota product administered rectally.

VOWST is an FDA-approved oral product containing purified bacterial spores derived from qualified human donor stool.

FDA approval means that a particular manufactured product has been evaluated for quality, safety, efficacy, and consistency for its labeled indication.

This does not mean that conventional FMT has become obsolete. Current gastroenterology guidelines continue to include conventional FMT among microbiota-based treatment options in appropriate recurrent C. difficile cases.

17. Does FMT permanently replace a person’s original microbiome with the donor’s microbiome?

No.

After FMT, some donor microorganisms may successfully establish themselves in the recipient — a process often called engraftment. Others may be present only temporarily.

The resulting microbiome is not simply a permanent copy of the donor’s.

It is shaped by interactions among:

  • the recipient’s original microbiota;
  • organisms introduced by treatment;
  • diet;
  • medications;
  • immune system;
  • age;
  • environment;
  • additional antibiotic exposure; and
  • other biological factors.

The intestinal microbiome remains dynamic throughout life.

Successful treatment therefore does not require the recipient’s microbiome to become identical to the donor’s. What seems to matter more is restoration of microbial functions and ecological stability sufficient to resist recurrence of disease.

18. What happens if a patient needs antibiotics again after successful FMT?

Antibiotics may again disrupt the intestinal microbiome and can increase the risk of recurrent C. difficile infection.

That does not mean a person who has had FMT should avoid antibiotics when they are medically necessary.

Instead, patients should tell future clinicians about their history of recurrent C. difficile infection and microbiota therapy. Clinicians can then consider:

  • whether an antibiotic is truly indicated;
  • whether a narrower-spectrum agent could be used;
  • the shortest appropriate duration;
  • the patient’s individual recurrence risk; and
  • whether any additional preventive strategy is warranted.

Antibiotic stewardship is particularly important in people who have already experienced recurrent C. difficile infection.

A previous successful FMT should therefore be considered part of the patient’s relevant medical history.

19. Why can’t donor screening eliminate all risk?

Screening greatly reduces risk, but it cannot reduce it to zero.

There are several reasons.

First, laboratory tests detect only organisms that are actually tested for.

Second, a donor may acquire an infection between screening visits.

Third, newly emerging pathogens may not yet be recognized as transmissible through stool.

Fourth, available tests may occasionally fail to detect an organism that is present.

The emergence of COVID-19 illustrates this problem. When SARS-CoV-2 first appeared, the implications of viral shedding in stool were not yet known. FDA subsequently added donor-screening and testing precautions specifically addressing the new virus.

Likewise, documented transmission of multidrug-resistant organisms prompted FDA to strengthen screening for MDRO risk factors and require additional testing.

Donor screening should therefore be viewed as an evolving risk-reduction system, not a guarantee that donor material is biologically risk-free.

20. Where is microbiome therapy heading beyond traditional FMT?

FMT helped demonstrate an important principle: changing a disturbed microbial ecosystem can sometimes produce a major clinical benefit.

The field is now trying to determine which organisms and microbial functions are actually necessary.

Future approaches may include:

  • carefully defined communities of cultured bacteria;
  • purified bacterial spores;
  • next-generation live biotherapeutic products;
  • bacteriophage-based treatments;
  • targeted manipulation of microbial metabolism;
  • engineered microorganisms;
  • personalized microbiome therapies; and
  • combinations of microbiota treatment with diet, drugs, or other interventions.

The approval of REBYOTA and VOWST represents an important step in this evolution from traditional donor-stool transplantation toward more standardized microbiota therapeutics.

However, enthusiasm about the microbiome should be balanced against evidence. For many diseases linked to microbiome changes, researchers still do not know whether those changes cause the disease, result from the disease, or both.

For that reason, FMT or other microbiome manipulation should not automatically be assumed to treat every disorder associated with an altered microbiome.

References

American Gastroenterological Association. (2024). Fecal microbiota-based therapies for select gastrointestinal diseases: Clinical practice guideline. Gastroenterology. https://doi.org/10.1053/j.gastro.2024.01.008.

American Gastroenterological Association. (2026). Management of Clostridioides difficile infection in inflammatory bowel disease. Gastroenterology.

Peery, A. F., Kelly, C. R., Kao, D., Vaughn, B. P., Lebwohl, B., Singh, S., Imdad, A., & Altayar, O. (2024). AGA clinical practice guideline on fecal microbiota-based therapies for select gastrointestinal diseases. Gastroenterology. https://doi.org/10.1053/j.gastro.2024.01.008.

U.S. Food and Drug Administration. (2019). Fecal microbiota for transplantation: Safety communication – Risk of serious adverse reactions due to transmission of multidrug-resistant organisms.

U.S. Food and Drug Administration. (2020a). Safety alert regarding use of fecal microbiota for transplantation and risk of serious adverse events likely due to transmission of pathogenic organisms.

U.S. Food and Drug Administration. (2020b). Safety alert regarding use of fecal microbiota for transplantation and additional safety protections pertaining to SARS-CoV-2 and COVID-19.

U.S. Food and Drug Administration. (2022a). Enforcement policy regarding investigational new drug requirements for use of fecal microbiota for transplantation to treat Clostridioides difficile infection not responsive to standard therapies: Guidance for industry.

U.S. Food and Drug Administration. (2022b). REBYOTA (fecal microbiota, live-jslm). U.S. Food and Drug Administration.

U.S. Food and Drug Administration. (2023a). VOWST (fecal microbiota spores, live-brpk). U.S. Food and Drug Administration.

U.S. Food and Drug Administration. (2023b). FDA approves first orally administered fecal microbiota product for the prevention of recurrence of Clostridioides difficile infection.

U.S. Food and Drug Administration. (n.d.). Fecal microbiota products. Center for Biologics Evaluation and Research.