Fecal Microbiota Transplantation (FMT)

Fecal Microbiota Transplantation: An Overview
The Evidence in Recurrent C. difficile Infection
FDA-Approved Fecal Microbiota Products
FMT Capsules in Cancer Immunotherapy Trials
FMT After Stem Cell Transplantation
Tracking Donor Bacteria After FMT
Expanding Applications: IBD, IBS, and Beyond
Next-Generation Microbiome Therapies
Key Research Papers
Connections
Featured Videos

Fecal Microbiota Transplantation: An Overview

Fecal microbiota transplantation (FMT) — the transfer of processed stool from a screened healthy donor into a patient's gastrointestinal tract — has its strongest evidence in recurrent Clostridioides difficile infection. Two fecal microbiota products made from donor stool have been approved by the U.S. Food and Drug Administration for preventing recurrence of that infection, and the FDA has also issued safety alerts about infections transmitted by FMT.

Outside C. difficile, FMT is being studied in cancer immunotherapy, stem cell transplantation, inflammatory bowel disease, irritable bowel syndrome, metabolic, autoimmune and neurological conditions. Most of that research consists of small or early-phase trials, and results so far have been mixed.

The Evidence in Recurrent C. difficile Infection

FMT's most established application is recurrent Clostridioides difficile infection (CDI). CDC surveillance published in 2015 estimated 453,000 C. difficile infections and about 29,300 deaths within 30 days of diagnosis in the United States in 2011. In a 2013 randomized trial in the New England Journal of Medicine, donor feces infused through a tube into the duodenum resolved C. difficile-associated diarrhea after the first infusion in 13 of 16 patients (81%), compared with 4 of 13 (31%) given vancomycin alone and 3 of 13 (23%) given vancomycin with bowel lavage; the trial was stopped early after an interim analysis.

The FMT National Registry, reporting real-world practice across North America in 2021, enrolled 259 participants at 20 sites; of the 222 with one-month follow-up, 200 (90%) were cured at one month, and 197 of those 200 (98%) had received only one FMT. Among 112 initially cured patients followed to six months, 4 (4%) had a recurrence. The 2024 American Gastroenterological Association (AGA) guideline suggests select use of fecal microbiota-based therapies after standard antibiotics to prevent recurrence in immunocompetent adults, and suggests against any of these therapies in severely immunocompromised adults.

A 2025 open-label randomized trial in Norway, published in the Annals of Internal Medicine, tested FMT against vancomycin in a first (primary) episode of CDI. Of 100 analyzed patients, 34 of 51 (66.7%) given FMT and 30 of 49 (61.2%) given vancomycin were cured with no recurrence within 60 days without further treatment, which met the trial's test for non-inferiority. The authors concluded that FMT "may be considered as first-line therapy in primary CDI."

Source: Cleveland Clinic Journal of Medicine — FMT: Current Evidence and Future Directions

FDA-Approved Fecal Microbiota Products

The FDA has approved two products prepared from donated human stool, both for preventing recurrence of C. difficile infection in adults after antibiotic treatment:

Fecal microbiota, live-jslm — approved on November 30, 2022, as "the first fecal microbiota product approved by the agency," given rectally as a single dose. In its phase 3 trial (PUNCH CD3, 267 treated patients), the original model estimated treatment success, defined as no C. difficile diarrhea within 8 weeks, at 70.4% versus 58.1% with placebo; after the data were aligned for the Bayesian analysis, the model estimate was 70.6% versus 57.5%.
Fecal microbiota spores, live-brpk — approved on April 26, 2023, as "the first fecal microbiota product that is taken orally": four capsules once a day for three consecutive days. In its phase 3 trial (ECOSPOR III, 182 enrolled patients), C. difficile recurred within 8 weeks in 12% of the treated group and 40% of the placebo group (the FDA gives 12.4% versus 39.8%).

The FDA's approval announcements state that, although donors and donated stool are tested for a panel of transmissible pathogens, both products may carry a risk of transmitting infectious agents and may contain food allergens.

FDA Safety Communications

On June 13, 2019, the FDA reported that two immunocompromised adults who received investigational FMT developed invasive infections with extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli, and that one of them died. Both FMT preparations came from the same donor, and the stool had not been tested for ESBL-producing organisms before use. The two cases were described in the New England Journal of Medicine in 2019, where genomic sequencing linked both infections to that donor.

On March 12, 2020, the FDA reported infections with enteropathogenic E. coli (EPEC) and Shiga toxin-producing E. coli (STEC) after investigational FMT supplied by a U.S. stool bank. In April 2020 it set out additional protections for investigational FMT, including nucleic acid testing of donor stool for EPEC and STEC, testing each donor before and after donations no more than 60 days apart, and quarantining untested stored product.

Source: American Gastroenterological Association — FDA Approves First FMT Therapy

FMT Capsules in Cancer Immunotherapy Trials

FMT is being tested alongside immune checkpoint inhibitors, cancer drugs that work through the immune system. Two trials published in Nature Medicine gave encapsulated stool from healthy donors to patients starting immunotherapy.

Lung Cancer and Melanoma

The phase 2 FMT-LUMINate trial, a multicenter open-label study, gave a single oral-capsule FMT before first-line immunotherapy to 20 patients with non-small cell lung cancer and 20 with melanoma. The objective response rate was 80% (16 of 20) in lung cancer, meeting the trial's primary endpoint, and 75% (15 of 20) in melanoma. An independent safety committee judged FMT safe in both groups; there were no grade 3 or higher adverse events in the lung cancer group, while 13 melanoma patients (65%), who received a two-drug immunotherapy combination, had grade 3 or higher adverse events. The abstract does not describe a comparison group that did not receive FMT.

Kidney Cancer

The phase 1 PERFORM trial gave encapsulated healthy-donor FMT with immunotherapy to 20 previously untreated patients with metastatic renal cell carcinoma. Its primary endpoint was safety, which was met: 10 of 20 patients (50%) had grade 3 immune-related adverse events, and there were no serious FMT-related toxicities and no grade 4 or 5 immune-related events. The objective response rate was 50% (9 of 18 evaluable patients), including two complete responses. The authors reported that most responders did not develop grade 3 or higher immune-related events, and that improved microbial diversity and durable engraftment of certain taxa correlated with less toxicity and better response.

The trials were led by researchers at the London Health Sciences Centre Research Institute, Lawson Research Institute, and the Centre de recherche du Centre hospitalier de l'Université de Montréal. The FMT-LUMINate authors wrote that their findings "confirm the clinical activity of FMT in combination with ICI" (immune checkpoint inhibitors); the PERFORM authors wrote that theirs "demonstrate the safety and potential" of functional microbiome engraftment. Each trial had 20 patients per cancer type.

Source: Medical Xpress — Fecal Transplant Capsules Show Promising Results in Cancer Clinical Trials (January 2026)

FMT After Stem Cell Transplantation

A trial led by Dr. Armin Rashidi at Fred Hutch Cancer Center, published in Nature Communications in January 2025, is testing whether healthy-donor FMT early after allogeneic stem cell transplantation reduces severe acute graft-versus-host disease (GVHD). The paper reports the single-arm run-in phase, in which 20 patients in three cohorts each received FMT from a different donor, to pick the donor for the randomized phase. The authors reported that FMT was safe and restored microbiota diversity.

Donor 3 yielded a median engraftment rate of 66%, higher than donors 1 and 2 (the center's news release gives 67% and describes this donor as having high levels of Bifidobacterium adolescentis)
Three patients developed severe acute GVHD, all of whom had received FMT from donor 1
According to the center's release, the capsules were taken three times a day for seven days, the transfer "did not cause any infections," and lower pre-FMT microbiota diversity was associated with better engraftment

Donor 3 was selected as the sole donor for the randomized phase, which the center's release describes as 126 patients randomly assigned to FMT from that donor or placebo.

Source: Fred Hutch Cancer Center — FMT After Stem Cell Transplantation (January 2025)

Tracking Donor Bacteria After FMT

Researchers at the Icahn School of Medicine at Mount Sinai described a method called LongTrack, which uses long-read DNA sequencing to follow individual bacterial strains after FMT. The study was announced in October 2025 and appears in the December 2025 issue of Nature Microbiology. The authors reported higher precision and specificity than short-read approaches, especially when several strains of a species are present in the same sample.

The method uncovered 648 engrafted strains across six FMT cases involving recurrent C. difficile infection and inflammatory bowel disease
Long reads allowed the team to assess engrafted strains at a 5-year follow-up, revealing structural variations that may be associated with adaptation to a new host

Gang Fang, PhD, the paper's senior author, said in the institution's release that the approach can "follow donor bacteria strain by strain with a level of reliability and scalability that wasn't possible before." The release describes the work as a step toward identifying microbial mixtures that could replace whole-stool transplants with treatments that are more predictable and easier to regulate.

Source: Mount Sinai — Scientists Develop Way to Track Donor Bacteria After FMT (October 2025)

Expanding Applications: IBD, IBS, and Beyond

FMT research is exploring a range of conditions linked to disrupted gut microbial communities. Outside C. difficile, the 2024 AGA guideline "suggests against the use of conventional fecal microbiota transplant as treatment for inflammatory bowel diseases or irritable bowel syndrome, except in the context of clinical trials," and states that FMT "cannot yet be recommended in other gastrointestinal conditions."

Inflammatory Bowel Disease (IBD)

As summarized in the Cleveland Clinic Journal of Medicine, the AGA guideline's evidence review found that in aggregate data from nine randomized controlled trials, patients receiving FMT had clinical remission more often (32.8%) than control groups (16.3%; relative risk 1.95, 95% CI 1.17–3.26). The guideline nonetheless limits FMT for IBD to clinical trials.

Irritable Bowel Syndrome (IBS)

Earlier randomized trials of FMT in IBS pointed in both directions. A later phase 3 trial, REFIT2, published in The Lancet in September 2026, found no benefit of donor FMT over the patients' own stool in 450 adults with IBS; it is covered in Fecal Transplant Shows No Benefit in Phase 3 IBS Trial.

Other Areas Under Study

Metabolic syndrome and obesity — early trials of microbiome restoration for metabolic health
Autoimmune conditions — research on the gut-immune axis in diseases such as rheumatoid arthritis
Neurological disorders — research on the gut-brain axis in conditions such as Parkinson's disease and autism spectrum disorder
Chronic constipation — a 2025 meta-analysis of nine studies (245 patients) reported improvements in stool consistency, quality of life and symptom scores, while noting heterogeneous protocols and limited randomized-trial data

Source: Frontiers in Microbiology — FMT: Application Scenarios, Efficacy Prediction, and Factors Impacting Donor-Recipient Interplay (2025)

Next-Generation Microbiome Therapies

Research is also moving beyond whole-stool transplants toward more defined approaches:

Defined microbial consortia — specified mixtures of bacterial strains, intended to remove the variability of donor stool
Fecal virome transplantation (FVT) — transfer of the virus fraction of donor stool, an experimental approach in early study
Personalized FMT — donor-recipient matching based on microbiome profiling, aimed at improving engraftment
Oral capsule formulations — less invasive delivery, as used by the orally administered FDA-approved spore product and the capsule-based cancer and stem cell trials

Strain-level tracking methods such as LongTrack are one of the tools researchers describe for developing standardized microbial therapeutics to replace whole-stool FMT.

Source: PMC — What's New and What's Next in Fecal Microbiota Transplantation?

Sources

News Archive

Key Research Papers

van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, et al. (2013). Duodenal infusion of donor feces for recurrent Clostridium difficile. New England Journal of Medicine 368(5):407-415. — PubMed PMID: 23323867
Lessa FC, Mu Y, Bamberg WM, Beldavs ZG, Dumyati GK, Dunn JR, et al. (2015). Burden of Clostridium difficile infection in the United States. New England Journal of Medicine 372(9):825-834. — PubMed PMID: 25714160
Kelly CR, Yen EF, Grinspan AM, Kahn SA, Atreja A, Lewis JD, et al. (2021). Fecal Microbiota Transplantation Is Highly Effective in Real-World Practice: Initial Results From the FMT National Registry. Gastroenterology 160(1):183-192.e3. — PubMed PMID: 33011173
Juul FE, Bretthauer M, Johnsen PH, Samy F, Tonby K, Berdal JE, et al. (2025). Fecal Microbiota Transplantation Versus Vancomycin for Primary Clostridioides difficile Infection: A Randomized Controlled Trial. Annals of Internal Medicine 178(7):940-947. — PubMed PMID: 40523286
Khanna S, Assi M, Lee C, Yoho D, Louie T, Knapple W, et al. (2022). Efficacy and Safety of RBX2660 in PUNCH CD3, a Phase III, Randomized, Double-Blind, Placebo-Controlled Trial with a Bayesian Primary Analysis for the Prevention of Recurrent Clostridioides difficile Infection. Drugs 82(15):1527-1538. — PubMed PMID: 36287379
Feuerstadt P, Louie TJ, Lashner B, Wang EEL, Diao L, Bryant JA, et al. (2022). SER-109, an Oral Microbiome Therapy for Recurrent Clostridioides difficile Infection. New England Journal of Medicine 386(3):220-229. — PubMed PMID: 35045228
DeFilipp Z, Bloom PP, Torres Soto M, Mansour MK, Sater MRA, Huntley MH, et al. (2019). Drug-Resistant E. coli Bacteremia Transmitted by Fecal Microbiota Transplant. New England Journal of Medicine 381(21):2043-2050. — PubMed PMID: 31665575
Peery AF, Kelly CR, Kao D, Vaughn BP, Lebwohl B, Singh S, et al.; AGA Clinical Guidelines Committee (2024). AGA Clinical Practice Guideline on Fecal Microbiota-Based Therapies for Select Gastrointestinal Diseases. Gastroenterology 166(3):409-434. — PubMed PMID: 38395525
Duttagupta S, Messaoudene M, Hunter S, Desilets A, Jamal R, Mihalcioiu C, et al. (2026). Fecal microbiota transplantation plus immunotherapy in non-small cell lung cancer and melanoma: the phase 2 FMT-LUMINate trial. Nature Medicine 32(4):1337-1350. — PubMed PMID: 41606121
Fernandes R, Jabbarizadeh B, Rajeh A, Hong MMY, Baines KJ, Ernst S, et al. (2026). Fecal microbiota transplantation plus immunotherapy in metastatic renal cell carcinoma: the phase 1 PERFORM trial. Nature Medicine 32(4):1325-1336. — PubMed PMID: 41606120
Reddi S, Senyshyn L, Ebadi M, Podlesny D, Minot SS, Gooley T, et al. (2025). Fecal microbiota transplantation to prevent acute graft-versus-host disease: pre-planned interim analysis of donor effect. Nature Communications 16(1):1034. — PubMed PMID: 39863610
Fan Y, Ni M, Aggarwala V, Mead EA, Ksiezarek M, Cao L, et al. (2025). Long-read metagenomics for strain tracking after faecal microbiota transplant. Nature Microbiology 10(12):3258-3271. — PubMed PMID: 41125958
Wang K, Gao C, Zhu L, Chen M, Tong YX, Zhang S (2025). Fecal microbiota transplantation for chronic constipation: a systematic review and meta-analysis of clinical efficacy, safety, and microbial dynamics. Frontiers in Microbiology 16:1604571. — PubMed PMID: 40822387
Johnsen PH, Juul FE, Hoff DAL, Hillestad ER, Holme Ø, Skjevling LK, et al. (2026). Faecal microbiota transplantation in irritable bowel syndrome (REFIT2): a randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet, published online September 24, 2026. — PubMed PMID: 42785338

— March 2, 2026 · Fecal Microbiota Transplantation

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