Protocol · graded by use, three uses
Fecal microbiota transplantation (FMT)
Recurrent C. difficile infection, adults.
At a glance
This page is about putting stool from a healthy donor into a patient's gut. It works well for one thing: a gut infection called C. difficile that keeps coming back after antibiotics. In trials, most patients were cured, far more than with antibiotics alone. For blood sugar, small early changes faded within months, and weight did not change. No finished trial has tested it on aging. Donor stool can carry germs, and one patient died of an infection passed on this way.
The A belongs to one of the three uses graded on this record. The other two carry their own letters.
This record carries a separate letter for each thing it has been measured on. The headline grade is the best of them, and it does not transfer to the others.
Five randomized trials from independent groups in four countries compared donor stool with antibiotics or with the patient's own stool. Four found more resolution with FMT (PMIDs PubMed ID: the permanent number the US National Library of Medicine gives a published paper. Each one links to that paper's record on PubMed. 23323867, 25728808, 27547925, 30610862); one, a single enema during an acute recurrence, did not (PMID 28011612). Minkoff et al. (Cochrane, 2023; PMID 37096495) pooled 6 trials and concluded that FMT likely leads to a large increase in resolution in immunocompetent adults. Cure of an infection is a clinical endpoint The outcome a trial measures to decide whether the treatment worked, such as heart attacks, blood pressure or a symptom score.. The grade belongs to adults with recurrent infection and does not transfer to healthy people. SER-109, a purified spore product, is a different agent and is listed in the sources, not counted here (PMID 35045228).
Vrieze et al. (2012; PMID 22728514) found insulin sensitivity higher 6 weeks after lean-donor FMT in men with metabolic syndrome, and Kootte et al. (2017; PMID 28978426), the same group, found the gain gone by 18 weeks. FMT-TRIM (Yu et al., 2020; PMID 32150549), double-blind Neither the participants nor the people assessing them know who received the real treatment until the trial ends. with capsules, found no significant improvement in clamp-measured insulin sensitivity, and Gut Bugs (Leong et al., 2020; PMID 33346848) found no effect on body mass index or insulin sensitivity in adolescents. Pooled, Qiu et al. (2023; PMID 37471410) found short-term gains in HbA1c A blood test that reflects average blood sugar over the previous two to three months., insulin and HDL with no lasting effect and no weight loss, and Zhang et al. (2025; PMID 41473248), pooling 11 trials, found no statistically significant Unlikely to be explained by chance alone at the threshold the study set. It says nothing about whether the difference is large enough to matter. improvement. A 4-year unblinded follow-up of Gut Bugs (PMID 40877311) found smaller waists and lower C-reactive protein with no difference in body mass index; it was not blinded and kept 55 of 87 participants. Insulin sensitivity, HbA1c and lipids are markers, which cap a grade at B, and the trials disagree, so the letter is C.
No randomized trial has reported the effect of FMT on an aging outcome in people. The first randomized trial in older adults (NCT06649981) is double-blind and placebo-controlled, testing capsules from young physically active donors in adults aged 65 to 84, with safety, functional autonomy and muscle strength as primary outcomes; only its protocol is published. Lifespan and rejuvenation findings come from animal studies, which carry no letter on this site. Route 1 No human randomized trial has been run, so the record rests on animal or mechanistic evidence only. One of the two routes to the lowest letter on EBL's scale.: the trial has not reported.
Recurrent C. difficile infection (A): donor stool cured recurrent infection more often than antibiotics in randomized trials from independent groups. Insulin sensitivity and other metabolic markers in metabolic syndrome and obesity are C: early gains faded and pooled trials were inconsistent. Aging and longevity are D: no randomized trial has reported results on an aging outcome.
Why this letter
Why this gradeThe reasoning, and what the grade does not cover.
Grade A, the record's best use: resolution of recurrent C. difficile infection in adults. Van Nood et al. (N Engl J Med, 2013; PMID 23323867), in Amsterdam, found donor feces resolved infection in 81 percent after one infusion against 31 and 23 percent with antibiotic arms; Cammarota et al. (2015; PMID 25728808), an independent group in Rome, found 90 against 26 percent with vancomycin; and Hvas et al. (2019; PMID 30610862), in Aarhus, found 92 against 42 percent with fidaxomicin and 19 percent with vancomycin. Kelly et al. (2016; PMID 27547925), blinded against the patient's own stool, found cure in 90.9 against 62.5 percent. Minkoff et al. (Cochrane, 2023; PMID 37096495) pooled 6 trials and concluded that FMT likely leads to a large increase in resolution. Cure of infection is a clinical endpoint and the result replicates across independent groups, which qualifies the letter.
WHAT THIS GRADE DOES NOT COVERhealthy people, where no trial has measured a clinical outcome; insulin sensitivity and metabolic markers in metabolic syndrome and obesity, graded C because early gains faded by 18 weeks (PMID 28978426) and pooled trials were inconsistent (PMIDs 37471410, 41473248); body mass index, which did not differ in any trial that measured it; and aging, frailty and longevity, graded D because no randomized trial has reported results (the first, NCT06649981, has published only its protocol). A single enema during an acute recurrence did not beat a vancomycin taper (PMID 28011612). SER-109, an approved purified spore product, is a different agent from donor stool and is not counted toward this letter (PMID 35045228).
Shared endpoint: Resolution of recurrent C. difficile infection without further recurrence, donor FMT against antibiotic treatment or the patient's own stool
- Academic Medical Center, University of Amsterdam, Netherlands (van Nood, Keller): Duodenal donor feces after a short vancomycin course resolved infection in 13 of 16 patients (81 percent) after one infusion, against 4 of 13 with vancomycin alone and 3 of 13 with vancomycin and bowel lavage; stopped early at interim analysis. PMID 23323867 · Funding: academic; no funding statement in the indexed record
- Catholic University, Rome, Italy (Cammarota, Gasbarrini): FMT by colonoscopy resolved infection in 18 of 20 patients (90 percent) against 5 of 19 (26 percent) with vancomycin; stopped early at interim analysis. PMID 25728808 · Funding: academic; no funding statement in the indexed record
- Aarhus University Hospital, Denmark (Hvas, Dahlerup): Clinical resolution in 92 percent with FMT against 42 percent with fidaxomicin and 19 percent with vancomycin; 64 adults. PMID 30610862 · Funding: academic; no funding statement in the indexed record
What the replication does not cover: The trials are small, open label against antibiotics, and two stopped early because FMT was clearly ahead, which can overstate an effect. Kelly et al. (PMID 27547925), blinded against the patient's own stool, found a smaller margin (90.9 against 62.5 percent). One trial in an acute recurrence found no benefit from a single enema against a vancomycin taper (Hota et al., PMID 28011612). The Cochrane review (PMID 37096495) pooled 6 trials and rated the evidence moderate certainty in immunocompetent adults.
A grade describes the human evidence for a named use. It is not advice, and it is not a judgment on any individual prescription. How the letters are decided →
Evidence notes: randomized trial, meta-analysis A study that pools the numbers from several trials into one combined estimate.
Endpoint graded: Resolution of recurrent C. difficile infection without further recurrence (hard)
Last reviewed: October 2026
Dose, form and timing
Measured outcome in the C. difficile trials: diarrhea resolved without a positive C. difficile test or further antibiotics, over about 8 to 10 weeks. In the metabolic trials, insulin sensitivity was measured by hyperinsulinemic euglycemic clamp in a research unit, which a person cannot check at home; HbA1c and fasting lipids are standard laboratory tests. No trial has measured an aging outcome.
As studiedDose, form, population and duration for every use.
A grade describes the intervention that was tested. Where the product on the shelf differs from it, this says so.
Safety
Infection from the donor: two patients in two separate clinical trials developed drug-resistant E. coli bloodstream infection, both traced by genomic sequencing to the same stool donor, and one died; the authors called for enhanced donor screening (DeFilipp 2019; PMID 31665575). The Cochrane conclusion applies to adults with normal immune function; too few immunocompromised participants were enrolled to judge risk or benefit in them (PMID 37096495).
Grade history
How this letter has changedLatest: No. 363 · October 2026 · First graded.
Fecal microbiota transplantation, stool from a screened donor placed in a patient's gut, now has a graded record. For recurrent C. difficile infection it is Grade A: randomized trials from independent groups in Amsterdam, Rome and Aarhus found far more cures than with antibiotics, and a Cochrane review of 6 trials concluded it likely leads to a large increase in resolution (Minkoff et al., Cochrane Database Syst Rev, 2023; PMID 37096495). For insulin sensitivity and metabolic markers in metabolic syndrome and obesity it is Grade C: an early gain was gone by 18 weeks (Kootte et al., Cell Metab, 2017; PMID 28978426), and a pooled analysis of 11 trials found no statistically significant improvement (Zhang et al., Front Endocrinol, 2025; PMID 41473248). For aging and longevity it is Grade D: no randomized trial has reported results.PMID 37096495 PMID 28978426 PMID 41473248
Every change to a letter on this site is dated and published. The full evidence log →
Sources
- Citations
- Every paper cited on this page is matched to its PubMed record on every build.
- Retractions
- None of these papers is retracted or under a journal expression of concern. PubMed is checked again on every build.
- Read against the papers
- October 2026. By a language model (AI-assisted reading), not yet reviewed by a clinician.
- Outside review
- Not yet done. No reviewer outside EBL has checked this record.
What each of these checks can and cannot show: evidence integrity.
The evidence, in full15 papers, each linked to its PubMed record.
Recurrent C. difficile, primary trials: van Nood et al. (N Engl J Med, 2013; PMID 23323867), Academic Medical Center, Amsterdam; duodenal infusion of donor feces after a short vancomycin course against vancomycin alone or vancomycin with bowel lavage; resolution in 13 of 16 (81 percent) after the first infusion against 4 of 13 and 3 of 13; stopped early at interim analysis. Cammarota et al. (Aliment Pharmacol Ther, 2015; PMID 25728808), Catholic University, Rome; FMT by colonoscopy against vancomycin; resolution in 18 of 20 (90 percent) against 5 of 19 (26 percent); stopped early at interim analysis. Kelly et al. (Ann Intern Med, 2016; PMID 27547925), Brown University and Montefiore Medical Center, NIH funded; donor FMT against the patient's own stool by colonoscopy in 46 adults with 3 or more recurrences; cure 20 of 22 (90.9 percent) against 15 of 24 (62.5 percent). Hvas et al. (Gastroenterology, 2019; PMID 30610862), Aarhus University Hospital; FMT against fidaxomicin or vancomycin in 64 adults; clinical resolution 92 against 42 and 19 percent. Hota et al. (Clin Infect Dis, 2017; PMID 28011612), Toronto; a single FMT enema after vancomycin against a vancomycin taper during an acute recurrence; recurrence 56.2 against 41.7 percent, stopped for futility. Pooled: Minkoff et al. (Cochrane Database Syst Rev, 2023; PMID 37096495), 6 randomized trials, 320 participants; in immunocompetent adults with recurrent infection, FMT likely leads to a large increase in resolution. Purified microbiome product, a different agent: Feuerstadt et al. (N Engl J Med, 2022; PMID 35045228), SER-109, oral purified Firmicutes spores, phase 3, 182 adults; recurrence 12 against 40 percent with placebo An inactive substitute made to look like the real treatment, so participants cannot tell which one they received. at 8 weeks; company sponsored. Metabolic syndrome and obesity: Vrieze et al. (Gastroenterology, 2012; PMID 22728514), lean-donor FMT against the recipient's own stool in men with metabolic syndrome; peripheral insulin sensitivity higher at 6 weeks. Kootte et al. (Cell Metab, 2017; PMID 28978426), same group; insulin sensitivity improved at 6 weeks and no metabolic change remained at 18 weeks; the response depended on the recipient's baseline microbiota. Yu et al. (PLoS Med, 2020; PMID 32150549), FMT-TRIM, double-blind, weekly lean-donor FMT capsules against placebo for 6 weeks in adults with obesity; donor microbes engrafted and insulin sensitivity measured by clamp did not improve significantly (mean difference 9 percent, 95% CI -5 to 28). Leong et al. (JAMA Netw Open, 2020; PMID 33346848), Gut Bugs, 87 adolescents with obesity, double-blind, capsules against placebo; no effect on body mass index at 6 weeks, the primary outcome, and no effect on insulin sensitivity; fewer participants with metabolic syndrome at 26 weeks in a post hoc analysis. Wilson et al. (Nat Commun, 2025; PMID 40877311), unblinded 4-year follow-up of 55 of the 87 Gut Bugs participants; no difference in body mass index; smaller waist, lower body fat, lower C-reactive protein and higher HDL cholesterol in the FMT group. Pooled: Qiu et al. (PLoS One, 2023; PMID 37471410), 9 studies, 303 participants; HbA1c, insulin and HDL improved within 6 weeks, no longer-term effect and no weight reduction. Zhang et al. (Front Endocrinol, 2025; PMID 41473248), 11 randomized trials, 320 participants; improvements did not reach statistical significance and HbA1c did not change. Aging: the published protocol of NCT06649981 describes a randomized, double-blind, placebo-controlled trial of capsules from young physically active donors in adults aged 65 to 84; primary outcomes safety, tolerability, functional autonomy and muscle strength; no results published. Safety: DeFilipp et al. (N Engl J Med, 2019; PMID 31665575), drug-resistant E. coli bacteremia in two patients after FMT in two separate trials, both linked by genomic sequencing to the same stool donor; one died.
How EBL searched for the trials (1 search)
The search that was run, what it returned, and what was left out and why, so the absence of evidence can be checked as well as its presence.
("fecal microbiota transplantation"[tiab] OR "fecal microbiota transplantation"[tiab] OR "fecal transplant"[tiab] OR "fecal transplant"[tiab] OR "donor feces"[tiab] OR "donor stool"[tiab]) AND ("Clostridioides difficile"[tiab] OR "Clostridium difficile"[tiab] OR "metabolic syndrome"[tiab] OR obesity[tiab] OR "insulin sensitivity"[tiab]) AND (randomized controlled trial[pt] OR meta-analysis[pt])Disclosure
Educational use only · Not medical advice · EBL grades published human evidence and does not recommend treatment. Stopping a prescription is a decision for your physician.
Evidence Based Longevity, Inc. is owner-operated and edited by Arnold Sandlow, D.C., a California-licensed chiropractor. Evidence Based Longevity publishes in English only · Machine translations are not produced or reviewed by EBL for accuracy
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