Fecal microbiota transplantation: what it is, how it is done, when it works and what the risks are

Fecal microbiota transplantation consists of transferring the stool of a healthy donor, suitably prepared, into a patient's gut. It sounds strange, but it is a real treatment, tested in randomized trials and included in guidelines for one specific infection: Clostridioides difficile infection that keeps coming back despite antibiotics. For many other diseases, however, it is still experimental. Let us look at what we know, how it is performed, what risks it carries and what the rules are in the United States and the United Kingdom.

What the gut microbiota is

Trillions of microorganisms live in the gut, especially in the colon: bacteria, viruses, fungi. Together they make up the gut microbiota. They are not passive guests: they help digest fiber, produce some vitamins, train the immune system and take up the space that would otherwise be taken by dangerous germs.

When this balance breaks down, it is called dysbiosis. The best-known cause is antibiotics, which eliminate the useful bacteria along with the harmful ones. It is precisely in a gut depleted by antibiotics that Clostridioides difficile finds room to multiply.

Why a stool transplant

Clostridioides difficile (once called Clostridium difficile) is a bacterium that produces toxins and causes diarrhea and colitis, sometimes severe, especially in older people, people in hospital or people who have taken antibiotics. The usual treatment is a targeted antibiotic, such as vancomycin or fidaxomicin. The problem is that in some patients the infection comes back, and each recurrence makes the next one more likely: the antibiotic kills the bacterium, but it does not rebuild the microbiota that should keep it in check.

The transplant does exactly that. Instead of adding one or two strains, as probiotics do, it transfers an entire ecosystem that is already balanced, which goes back to occupying the gut and prevents Clostridioides from taking over again.

How it is performed

Choosing the donor

This is the most delicate part, because infections can be transmitted with stool. European and international consensus documents provide for several steps:

• a questionnaire on health and lifestyle, which excludes anyone who has taken antibiotics in the last three months, anyone with intestinal, autoimmune or metabolic diseases and anyone with behaviors that carry a risk of infection;
• blood tests for hepatitis A, B, C and E, HIV, syphilis and some parasites, as well as a complete blood count and liver and kidney function;
• stool tests for Clostridioides difficile, pathogenic intestinal bacteria, antibiotic-resistant bacteria, intestinal viruses and parasites;
• a new questionnaire on the day of each donation and periodic repetition of the tests in regular donors.

The selection is strict: in a large US stool bank about nine candidates out of ten are excluded. This is another reason why microbiota banks (stool banks) are preferred today: they prepare and freeze material from donors who have already been screened.

Preparation

The stool is diluted, filtered and used fresh, or frozen and stored until use. The patient usually first completes a course of antibiotic against Clostridioides and does a bowel preparation, as for a colonoscopy.

Routes of administration

• Colonoscopy: the material is placed in the colon during the examination. In Italy, it was the route used in all the transplants recorded by the Italian National Transplant Centre between 2020 and 2023.
• Capsules to swallow: they contain freeze-dried or frozen microbiota. In a randomized trial of 116 patients, capsules worked as well as colonoscopy: no recurrence in 96% of cases in both groups.
• Enema or a tube passed through the nose and stomach down to the duodenum: used in some studies, less common today. The upper routes, through the nose or mouth, are the ones to which a review of the studies attributes most of the rare deaths linked to the transplant.

When it works: recurrent Clostridioides difficile infections

This is the only established indication.

• In the first randomized trial, published in 2013, the transplant cured 13 patients out of 16 (81%) after the first infusion, compared with 31% with vancomycin alone. The trial was stopped early because the difference was clear.
• In an Italian study from 2015, 90% of patients were cured with the transplant by colonoscopy, compared with 26% with vancomycin.
• The 2023 Cochrane review, which pooled 6 randomized trials with 320 adults, concludes that the transplant roughly doubles the cure rate compared with the comparison treatments: treating three patients is enough for one more to be cured. The certainty of the evidence is rated moderate.

Guidelines include it after at least two recurrences, together with antibiotics. The strength of the recommendation, however, is not the same everywhere: strong for the American infectious diseases (2017) and gastroenterology (2021) societies and for the 2017 European consensus, weak for the European society of clinical microbiology (2021). In 2024 the American Gastroenterological Association confirmed it as an option in adults after recurrences, advising against it in people with a severely compromised immune system.

A Norwegian study from 2025 tried the transplant already at the first infection, instead of vancomycin, with similar results (67% versus 61% cured without recurrence). It is a single study of 100 patients: for now the first choice remains the antibiotic.

Areas still under study

Here the evidence is much weaker and, in some cases, negative.

• Ulcerative colitis: the 2023 Cochrane review (10 studies, 468 patients) indicates that the transplant may increase clinical remission, but the certainty is low. It is not clear how long the effect lasts.
• Crohn's disease: there are no randomized trials on inducing remission; for maintenance there is only one, with 21 patients. Certainty very low.
• Irritable bowel syndrome: the first small studies had given conflicting results. In 2026 the largest phase 3 trial, carried out in Norway in 448 patients, found no difference: 40% improved with the transplant and 38% with placebo. A meta-analysis from the same year rates the evidence of benefit as of very low certainty.
• Other fields: hepatic encephalopathy in cirrhosis (one small randomized trial), cancers treated with immunotherapy, such as melanoma (phase 1 and 2 studies), metabolic syndrome and autism (small studies, often without a control group). These are interesting hypotheses, not treatments: the 2024 American guidelines advise against the transplant for inflammatory bowel diseases and irritable bowel syndrome outside clinical trials.

The same idea is also being studied outside the gut: vaginal microbiota transplantation, proposed for vaginosis that keeps coming back, is even more experimental and today is done only within clinical trials.

Risks and safety

In most cases the transplant is well tolerated. A review of 129 studies with more than 4,200 patients found adverse effects in 19% of procedures, almost always mild and short-lived: diarrhea, cramps, bloating, low-grade fever. Serious events occurred in 1.4%.

The most feared risk is the transmission of an infection from the donor. In 2019, in the United States, two frail patients enrolled in clinical trials developed a bloodstream infection with antibiotic-resistant Escherichia coli, transmitted with the stool of the same donor, who had not been screened for those bacteria; one of the two died. Since then, testing for resistant bacteria has become a standard part of donor screening. In Italy, in the 214 transplants recorded from 2020 to 2023, the Italian National Transplant Centre reported no serious adverse reactions.

Long-term effects remain poorly understood, because the microbiota influences metabolism and immunity: this is why patients are followed up over time.

Where it is done and what the rules are in the United States and the United Kingdom

In the United States, fecal microbiota products used to prevent or treat a disease are biological products overseen by the FDA (FDA page, content current as of 07/06/2023, consulted on 23/10/2026). Outside clinical trials, the FDA has stated in a final guidance of November 2022 that it intends to exercise enforcement discretion over investigational new drug requirements only for the use of fecal microbiota transplantation to treat Clostridioides difficile infection not responding to standard therapies, provided that the treating doctor obtains adequate consent from the patient; this policy does not apply to material obtained from a stool bank (consulted on 23/10/2026). Standardized industrial products based on microbiota, by contrast, are medicines: the FDA has approved two to prevent recurrences of Clostridioides in adults after antibiotic treatment for a recurrence, one given rectally (30 November 2022) and one in capsules (26 April 2023).

In the United Kingdom, fecal microbiota transplantation is supplied either through clinical trials or as an unlicensed medicine, under the MHRA's "specials" manufacturing arrangements or by extemporaneous preparation, and no microbiome-based medicinal product currently holds a UK marketing authorisation (MHRA, 18 August 2026, consulted on 23/10/2026). NICE recommends fecal microbiota transplantation as an option to treat recurrent Clostridioides difficile infection in adults who have had 2 or more previous confirmed episodes (HealthTech guidance HTG638, formerly MTG71, published on 31 August 2022, consulted on 23/10/2026).

Access is on the recommendation of a specialist, a gastroenterologist or an infectious disease specialist, who assesses whether the patient meets the requirements. The Italian data cited in this article come from the Italian national program, coordinated since 2018 by the Italian National Transplant Centre, which allows the transplant only for Clostridioides difficile infections resistant to antibiotic therapy and listed 10 authorized centers in its 2023 report.

Why it should never be done at home

Instructions for "do-it-yourself" transplants circulate on the internet, with the stool of a relative or friend, blended and given with an enema. It is a dangerous practice, for several reasons:

• without the tests described above there is no way of knowing whether the donor carries viruses, parasites or resistant bacteria, which often cause no symptoms;
• even a donor who feels well may have a recently acquired infection;
• there is no control at all over preparation and storage;
• a badly performed enema or tube can injure the bowel;
• often the initial diagnosis has not been made, and the symptoms may hide a disease that needs other treatments.

Clinics that offer the transplant for unrecognized indications, outside authorized centers and registered studies, should also be avoided. Anyone who has a Clostridioides infection that keeps coming back, or a chronic bowel disease, should talk to their specialist, who can point them to an authorized center or a clinical trial.

Frequently asked questions

Does fecal microbiota transplantation hurt?

No. Colonoscopy is usually done under sedation, and capsules simply have to be swallowed. In the following days mild bloating or diarrhea may appear.

Does it help you lose weight or treat irritable bowel syndrome?

No. For weight there is no evidence of effectiveness, and the largest study on irritable bowel syndrome was negative.

Is it the same as probiotics?

No. A probiotic contains a few selected strains; the transplant transfers the entire community of microorganisms of a donor.

Can I choose the donor myself?

No. The donor is chosen and screened by the center, with the tests described above; more and more often, frozen material from stool banks is used.

References

1. van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013. PubMed
2. Cammarota G, Masucci L, Ianiro G, Bibbò S, Dinoi G, Costamagna G, et al. Randomised clinical trial: faecal microbiota transplantation by colonoscopy vs. vancomycin for the treatment of recurrent Clostridium difficile infection. Aliment Pharmacol Ther. 2015. PubMed
3. Minkoff NZ, Aslam S, Medina M, Tanner-Smith EE, Zackular JP, Acra S, et al. Fecal microbiota transplantation for the treatment of recurrent Clostridioides difficile (Clostridium difficile). Cochrane Database Syst Rev. 2023. PubMed
4. Kao D, Roach B, Silva M, Beck P, Rioux K, Kaplan GG, et al. Effect of oral capsule- vs colonoscopy-delivered fecal microbiota transplantation on recurrent Clostridium difficile infection: a randomized clinical trial. JAMA. 2017. PubMed
5. Juul FE, Bretthauer M, Johnsen PH, Samy F, Tonby K, Berdal JE, et al. Fecal microbiota transplantation versus vancomycin for primary Clostridioides difficile infection: a randomized trial. Ann Intern Med. 2025. PubMed
6. McDonald LC, Gerding DN, Johnson S, Bakken JS, Carroll KC, Coffin SE, et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by IDSA and SHEA. Clin Infect Dis. 2018. PubMed
7. Kelly CR, Fischer M, Allegretti JR, LaPlante K, Stewart DB, Limketkai BN, et al. ACG clinical guidelines: prevention, diagnosis, and treatment of Clostridioides difficile infections. Am J Gastroenterol. 2021. PubMed
8. van Prehn J, Reigadas E, Vogelzang EH, Bouza E, Hristea A, Guery B, et al. European Society of Clinical Microbiology and Infectious Diseases: 2021 update on the treatment guidance document for Clostridioides difficile infection in adults. Clin Microbiol Infect. 2021. PubMed
9. Peery AF, Kelly CR, Kao D, Vaughn BP, Lebwohl B, Singh S, et al. AGA clinical practice guideline on fecal microbiota-based therapies for select gastrointestinal diseases. Gastroenterology. 2024. PubMed
10. Cammarota G, Ianiro G, Tilg H, Rajilić-Stojanović M, Kump P, Satokari R, et al. European consensus conference on faecal microbiota transplantation in clinical practice. Gut. 2017. PubMed
11. Cammarota G, Ianiro G, Kelly CR, Mullish BH, Allegretti JR, Kassam Z, et al. International consensus conference on stool banking for faecal microbiota transplantation in clinical practice. Gut. 2019. PubMed
12. Imdad A, Pandit NG, Zaman M, Minkoff NZ, Tanner-Smith EE, Gomez-Duarte OG, et al. Fecal transplantation for treatment of inflammatory bowel disease. Cochrane Database Syst Rev. 2023. PubMed
13. Johnsen PH, Juul FE, Hoff DAL, Hillestad ER, Holme Ø, Skjevling LK, et al. Faecal microbiota transplantation in irritable bowel syndrome (REFIT2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2026. PubMed
14. Aumpan N, Watanabe J, Yuan Y, Kanno T, Leontiadis GI, Chan FKL, et al. Fecal microbiota transplantation for symptom improvement in patients with irritable bowel syndrome: systematic review and meta-analysis. Gastroenterology. 2026. PubMed
15. Marcella C, Cui B, Kelly CR, Ianiro G, Cammarota G, Zhang F. Systematic review: the global incidence of faecal microbiota transplantation-related adverse events from 2000 to 2020. Aliment Pharmacol Ther. 2021. PubMed
16. DeFilipp Z, Bloom PP, Torres Soto M, Mansour MK, Sater MRA, Huntley MH, et al. Drug-resistant E. coli bacteremia transmitted by fecal microbiota transplant. N Engl J Med. 2019. PubMed
17. Centro Nazionale Trapianti (Italian National Transplant Centre). Donare il microbiota (Donating microbiota). Updated on 25/06/2025, consulted on 22/10/2026. trapianti.salute.gov.it
18. Centro Nazionale Trapianti (Italian National Transplant Centre). Annual report on the activity of the Italian national transplant network 2023 (fecal microbiota transplantation, list of centers). Consulted on 22/10/2026. trapianti.salute.gov.it
19. U.S. Food and Drug Administration. Fecal Microbiota Products. Content current as of 07/06/2023, consulted on 23/10/2026. fda.gov
20. U.S. Food and Drug Administration. 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, final, November 2022 (docket FDA-2013-D-0811). Consulted on 23/10/2026. fda.gov
21. U.S. Food and Drug Administration. REBYOTA (fecal microbiota, live-jslm), approved on 30/11/2022. Consulted on 23/10/2026. fda.gov
22. U.S. Food and Drug Administration. FDA Approves First Orally Administered Fecal Microbiota Product for the Prevention of Recurrence of Clostridioides difficile Infection. Press release, 26/04/2023. Consulted on 23/10/2026. fda.gov
23. Medicines and Healthcare products Regulatory Agency (MHRA). MHRA sets out position on regulation of microbiome-based medicinal products. 18/08/2026. Consulted on 23/10/2026. gov.uk
24. National Institute for Health and Care Excellence (NICE). Faecal microbiota transplant for recurrent Clostridioides difficile infection. HealthTech guidance HTG638 (formerly MTG71), published on 31/08/2022. Consulted on 23/10/2026. nice.org.uk