Fecal microbiota transplantation (FMT): what it treats and what can go wrong

What it is

FMT transfers stool from a screened donor into a patient's gut, by colonoscopy, enema or capsules. Two regulator-approved products exist in the US: REBYOTA (fecal microbiota, live-jslm, rectal) and Vowst (oral), both to prevent recurrence of C. difficile infection after antibiotics.

What the research says

For recurrent Clostridioides difficile infection, a Cochrane review found FMT likely leads to a large increase in resolution (RR 1.92, moderate certainty), and an oral product cut 8-week recurrence to 12.4% versus 39.8% on placebo. For other conditions the evidence is weak or null: an IBS meta-analysis found no significant long-term global benefit, capsule FMT showed no effect in IBS, and FMT did not reduce weight in metabolic syndrome. Donor stool has transmitted drug-resistant E. coli (one death) and Shiga toxin-producing E. coli, prompting FDA screening requirements.

Evidence grade: Well established.

What goes wrong

Two immunocompromised trial patients developed ESBL-producing E. coli bacteremia after FMT from the same donor, confirmed by genomic sequencing; one died. (Source 1)

• Case series, Certainty not rated.
• Size: 2 patients.
• Who: immunocompromised adults in two clinical trials.
• How long: not applicable.
• Result: 1 death.
• Funding: American College of Gastroenterology grant.

both cases were linked to the same stool donor by means of genomic sequencing. One of the patients died.

After these cases, FDA (June 2019) required donor questioning about multidrug-resistant organism risk and MDRO testing of donor stool. (Source 2)

• Official position, Certainty not rated.
• Size: 2 patients.
• Who: recipients of investigational FMT.
• How long: not applicable.
• Result: 1 death.
• Funding: FDA position.

MDRO testing of donor stool and exclusion of stool that tests positive for MDRO

In March 2020 FDA reported six patients who developed E. coli infections (two EPEC, four Shiga toxin-producing STEC) after receiving one US stool bank's FMT product for C. difficile. (Source 3)

• Official position, Certainty not rated.
• Size: 6 infected patients.
• Who: patients receiving FMT for C. difficile.
• How long: not applicable.
• Result: 2 EPEC and 4 STEC infections.
• Funding: FDA position.

FDA has been notified of six patients who received the company's FMT product for Clostridium difficile

FDA said it suspects, but did not state as proven, that these infections were caused by transmission of the organisms from the stool bank's FMT product. (Source 4)

• Official position, Certainty not rated.
• Size: not applicable.
• Who: patients receiving FMT for C. difficile.
• How long: not applicable.
• Result: suspected transmission (not confirmed)
• Funding: FDA position.

that it suspects are due to transmission of these pathogenic organisms from FMT product supplied by a stool bank company based in the United States

Two further patients died after receiving FMT product from the donor linked to the STEC infections; FDA said it is not known whether STEC infection contributed to their deaths. (Source 5)

• Official position, Certainty not rated.
• Size: 2 deaths.
• Who: patients receiving FMT for C. difficile.
• How long: not applicable.
• Result: 2 deaths; contribution of STEC unknown.
• Funding: FDA position.

Additionally, the company notified the FDA of two patients who died following receipt of FMT product from the donor associated with the STEC infections.

A systematic review of 50 studies found adverse events and serious adverse events after FMT are not rare (overall adverse event incidence 28.5% as summarised on the page). (Source 6)

• Systematic review, Low certainty.
• Size: 50 studies.
• Who: FMT recipients, mixed indications.
• How long: varied.
• Result: AE incidence 28.5%; mortality 3.5% and infection 2.5% among SAEs (as summarised)
• Funding: not stated.

both AEs and SAEs are not rare and should be carefully monitored throughout FMT

Vowst's most common side effects more frequent than placebo were abdominal bloating, fatigue, constipation, chills and diarrhoea, and it may carry a risk of transmitting infectious agents. (Source 7)

• Official position, Certainty not rated.
• Size: not stated.
• Who: adults with recurrent CDI.
• How long: not applicable.
• Result: not stated.
• Funding: FDA position.

Vowst may carry a risk of transmitting infectious agents

What the evidence supports

In immunocompetent adults with recurrent C. difficile infection, FMT likely leads to a large increase in resolution compared with alternatives such as antibiotics. (Source 8)

• Systematic review, Moderate certainty.
• Size: 6 RCTs, 320 participants.
• Who: immunocompetent adults with recurrent CDI.
• How long: up to 8 weeks in most trials.
• Result: RR 1.92 (95% CI 1.36-2.71); NNTB 3.
• Funding: not stated on page fetched.

In immunocompetent adults with rCDI, FMT likely leads to a large increase in the resolution of recurrent Clostridioides difficile infection compared to alternative treatments such as antibiotics.

A 45-study meta-analysis including observational data rated evidence for repeat FMT as high quality and found effect varies with delivery route and number of doses. (Source 9)

• Meta-analysis, High certainty.
• Size: 45 studies.
• Who: patients with recurrent CDI.
• How long: 8 weeks.
• Result: 91% clinical effect after repeat FMT, 84% after single FMT (as summarised on the page)
• Funding: not stated on page fetched.

High-quality evidence supports FMT is effective for recurrent CDI, but its effect varies with the delivery method and the number of administrations.

FDA approved Vowst (2023), the first oral fecal microbiota product; in its trial 8-week CDI recurrence was 12.4% with Vowst versus 39.8% with placebo. (Source 7)

• Official position, Moderate certainty.
• Size: not stated on page.
• Who: adults with recurrent CDI.
• How long: 8 weeks.
• Result: 12.4% vs 39.8% recurrence.
• Funding: industry-sponsored trial (Seres); FDA position.

Through 8 weeks after treatment, CDI recurrence in Vowst-treated participants was lower compared to placebo-treated participants (12.4% compared to 39.8%)

REBYOTA is FDA-approved only to prevent C. difficile recurrence in adults after antibiotic treatment for recurrent CDI. (Source 10)

• Official position, Certainty not rated.
• Size: not applicable.
• Who: adults 18+.
• How long: not applicable.
• Result: not applicable.
• Funding: FDA position.

REBYOTA is indicated for the prevention of recurrence of Clostridioides difficile infection (CDI) in individuals 18 years of age and older

What the evidence does not support

In IBS, a meta-analysis of 10 RCTs found no significant difference between FMT and placebo in short- or long-term global symptom improvement. (Source 11)

• Meta-analysis, Low certainty.
• Size: 10 RCTs, 573 subjects.
• Who: adults with IBS.
• How long: 12-52 weeks.
• Result: no significant difference from placebo at 12 or 52 weeks (52 weeks RR 1.38, 95% CI 0.87 to 2.21); the paper's 12-week figure is internally inconsistent, see caveat.
• Funding: not stated.

Limit of this finding: The paper reports the 12-week result as 'RR 0.20, 95% CI -0.04 to 0.44'. A risk ratio cannot be negative, so this figure is internally inconsistent in the source (it may be a risk difference or a typo). Do not read it as a risk ratio or as evidence of harm; the safe conclusion is only that the authors found no significant short-term or long-term difference from placebo.

the current evidence does not support the efficacy of FMT in improving global IBS symptoms in the long term

In obesity/metabolic syndrome, FMT produced small short-term improvements in glucose markers but no significant weight reduction versus placebo. (Source 12)

• Meta-analysis, Low certainty.
• Size: 9 studies, 303 participants.
• Who: adults with obesity and/or metabolic syndrome.
• How long: <6 weeks for short-term outcomes.
• Result: HbA1c MD -0.37 mmol/mol; no significant difference in weight.
• Funding: not stated.

Limit of this finding: This meta-analysis reports its insulin result in mmol/L, which is not a normal unit for insulin, so that insulin figure should not be relied on. This finding uses only the weight and HbA1c results, which are not affected.

However, there was no significant difference between the FMT group and the placebo group in terms of weight reduction.

Where the evidence is mixed

The Cochrane review found no conclusive safety evidence for FMT in recurrent CDI because events were few. (Source 8)

• Systematic review, Low certainty.
• Size: 6 RCTs, 320 participants.
• Who: adults with recurrent CDI.
• How long: short term.
• Result: serious adverse events RR 0.73 (0.38-1.41); mortality RR 0.57 (0.22-1.45)
• Funding: not stated.

There was no conclusive evidence regarding the safety of FMT for the treatment of rCDI

Another IBS meta-analysis found single stool FMT reduced symptom scores (moderate-quality evidence) but capsule FMT showed no positive effect. (Source 13)

• Meta-analysis, Moderate certainty.
• Size: 9 RCTs.
• Who: adults with IBS.
• How long: 1-36 months.
• Result: IBS-SSS MD -102.11 at 3 months (95% CI -141.98 to -62.24); capsules no benefit.
• Funding: not stated.

However, we did not find positive effect of capsule FMT on patients with IBS based on the current available data.

Across 20 RCTs, serious adverse events were not significantly more frequent with microbiota transplantation than control, with wide confidence intervals. (Source 14)

• Meta-analysis, Low certainty.
• Size: 20 RCTs.
• Who: trial participants, mixed indications.
• How long: varied.
• Result: SAE RR 1.36 (95% CI 0.56-3.31)
• Funding: not stated.

Limit of this finding: In the same abstract the authors say 360 patients were in the common-adverse-event analysis but give group sizes of 195 and 166, which add up to 361. This is a small arithmetic inconsistency in the source; it does not change the serious-adverse-event result quoted here, but exact patient counts from this paper should be treated with some caution.

We found no significant difference in the incidence of SAEs between the IMT group and the control group (RR = 1.36, 95% CI 0.56–3.31, P = 0.50)

Where the research disagrees

Does FMT help irritable bowel syndrome?

• Wang et al. 2023 meta-analysis, meta-analysis of 9 RCTs: A single stool FMT reduced IBS-SSS; quality of evidence based on GRADE system was moderate in the stool FMT group (Source 13)
• Wang, Hu and Shi 2024 meta-analysis, meta-analysis of 10 RCTs: the current evidence does not support the efficacy of FMT in improving global IBS symptoms in the long term (Source 11)

A common belief, and what the research shows

The belief: Because FMT cures C. difficile, it can fix the microbiome for any condition.

What the research shows: The strong evidence is specific to recurrent C. difficile. For IBS "the current evidence does not support the efficacy of FMT in improving global IBS symptoms in the long term", and in metabolic syndrome "there was no significant difference between the FMT group and the placebo group in terms of weight reduction".

Questions and answers

What is it?

FMT is the transfer of donor stool into a patient's gut. It is an established therapy for recurrent C. difficile infection and is being studied for other conditions. (Source 1)

What does it do in the body?

In recurrent C. difficile infection, FMT restores resolution far more often than alternatives. Outside that use, benefits are inconsistent. (Source 8)

Is it good or bad for you?

Beneficial for recurrent C. difficile (moderate-to-high certainty). Risky if donor stool carries pathogens: drug-resistant E. coli transmitted by FMT caused bloodstream infections, and one patient died. FDA has also reported E. coli infections, including Shiga toxin-producing E. coli, that it suspects came from a stool bank's FMT product. (Source 1)

How do you get more of it?

FMT is given in medical settings; two FDA-approved products exist for preventing C. difficile recurrence in adults. Not a consumer intervention. (Source 10)

If it is harmful, what reduces it?

The harm of FMT is pathogen transmission; FDA's response was stricter donor screening, including testing donor stool for multidrug-resistant organisms. (Source 2)

Why might someone be low in it or missing it?

People reach FMT because repeated C. difficile infection follows antibiotic treatment; approved products are used after antibiotic treatment for recurrent CDI. (Source 10)

Which whole foods contain it or feed it?

Does not apply: FMT is a medical procedure, not a food. No whole food substitutes for it in the literature we searched. (Source 1)

What happens if you do not have it?

Without effective treatment, recurrent C. difficile often returns: in the Vowst trial 39.8% of placebo recipients recurred within 8 weeks. (Source 7)

How can you test for it, and how reliable is that test?

Testing applies to donors: stool is screened for transmissible pathogens and multidrug-resistant organisms, but screening does not remove all risk. (Source 7)

References

1. New England Journal of Medicine. Drug-Resistant E. coli Bacteremia Transmitted by Fecal Microbiota Transplant. 2019. PMID 31665575, DOI 10.1056/NEJMoa1910437. Read the source
2. US Food and Drug Administration. Important Safety Alert Regarding Use of Fecal Microbiota for Transplantation and Risk of Serious Adverse Reactions Due to Transmission of Multi-Drug Resistant Organisms. 2019. Read the source
3. US Food and Drug Administration. Safety Alert Regarding Use of Fecal Microbiota for Transplantation and Risk of Serious Adverse Events Likely Due to Transmission of Pathogenic Organisms. 2020. Read the source
4. US Food and Drug Administration. Safety Alert Regarding Use of Fecal Microbiota for Transplantation and Risk of Serious Adverse Events Likely Due to Transmission of Pathogenic Organisms. 2020. Read the source
5. US Food and Drug Administration. Safety Alert Regarding Use of Fecal Microbiota for Transplantation and Risk of Serious Adverse Events Likely Due to Transmission of Pathogenic Organisms. 2020. Read the source
6. PLOS ONE. Systematic Review: Adverse Events of Fecal Microbiota Transplantation. 2016. PMID 27529553, DOI 10.1371/journal.pone.0161174. Read the source
7. US Food and Drug Administration. FDA Approves First Orally Administered Fecal Microbiota Product for the Prevention of Recurrence of Clostridioides difficile Infection. 2023. Read the source
8. Cochrane Database of Systematic Reviews. Fecal microbiota transplantation for the treatment of recurrent Clostridioides difficile (Clostridium difficile). 2023. PMID 37096495, DOI 10.1002/14651858.CD013871.pub2. Read the source
9. EClinicalMedicine. Faecal microbiota transplantation for recurrent Clostridioides difficile infection: An updated systematic review and meta-analysis. 2020. DOI 10.1016/j.eclinm.2020.100642. Read the source
10. US Food and Drug Administration. REBYOTA (fecal microbiota, live-jslm). 2022. Read the source
11. BMC Gastroenterology. A meta-analysis of randomized controlled trials evaluating the effectiveness of fecal microbiota transplantation for patients with irritable bowel syndrome. 2024. DOI 10.1186/s12876-024-03311-x. Read the source
12. PLOS ONE. Effects of fecal microbiota transplantation in metabolic syndrome: A meta-analysis of randomized controlled trials. 2023. DOI 10.1371/journal.pone.0288718. Read the source
13. Frontiers in Immunology. Fecal microbiota transplantation for irritable bowel syndrome: a systematic review and meta-analysis of randomized controlled trials. 2023. DOI 10.3389/fimmu.2023.1136343. Read the source
14. Gut Pathogens. Adverse events of intestinal microbiota transplantation in randomized controlled trials: a systematic review and meta-analysis. 2022. DOI 10.1186/s13099-022-00491-3. Read the source