Scientific background · Obesity and metabolism

What microbiota transfer is based on in metabolic disease

This page is the reference background for the obesity and metabolism page. It works through thirteen publications — not mixed together, but by two endpoints: separately for body weight and separately for the metabolic markers. The evidence for the two is not the same, and that is precisely the message of this page.

What we know today, and what we do not

There are few fields where public discourse and clinical evidence have drifted this far apart. Behind the sentence “the gut flora makes you fat” there are real physiological observations — but of the claim that replacing the gut flora makes you lose weight, not a single randomised trial has demonstrated anything.

What this literature does support

That the gut microbiota has a say in metabolism has been well described at the level of mechanism: some species extract more energy from food and increase the permeability of the intestinal wall, others strengthen the gut barrier, and the short-chain fatty acids regulate lipid metabolism through receptors.810 On the clinical side the strongest observation is the temporary improvement in insulin sensitivity: six weeks after microbiota from a lean donor had been delivered into the small intestine, the glucose disappearance rate had measurably increased.194

The effect does not appear in everyone, and that in itself is informative: the response depends on the recipient's baseline gut flora — a low baseline diversity and the proportion of certain genera predict who will respond.712, 811 The accompanying intervention matters just as much: given together with fibre supplementation or a lifestyle intervention, the results were better than on its own.805, 806

What it does not support

Weight loss is not proven. The most recent meta-analysis pools nine randomised trials and 303 patients: for body weight the difference was 2.72 kg, with a confidence interval so wide (95% CI −4.74 … +10.18) that it includes both the absence of an effect and a change in either direction; the same applies to the body mass index.821 A 2025 analysis pooling eleven trials and 320 patients also found only a non-significant trend, and judged the strength of the evidence to be low.809

Durability is not established either. In the follow-up beyond twelve weeks the meta-analysis found no difference on any endpoint,821 and in the mechanism study the improvement at six weeks had disappeared by eighteen weeks.712 Only one longer-term dataset is available: in the four-year follow-up of a study in adolescents the body mass index did not differ, but the waist circumference was 10.0 cm, the body fat percentage 4.8 percentage points and the inflammatory marker 68 per cent more favourable.808 This is a single cohort, in a non-blinded follow-up — an interesting signal, not proof.

Finally, engraftment is not enough. In an American randomised trial the transplanted flora became durably established, yet insulin sensitivity, HOMA-IR and body weight did not improve significantly.804 This negative result is more important than it seems: it rules out the explanation that the absence of an effect is merely a technical failure.

Safety

The intervention was well tolerated in the studies. The meta-analysis found only mild events — a slight rise in temperature, headache, nausea, diarrhoea, abdominal pain — no serious side effect was described, and the authors assess the intervention as an adjunctive treatment.821 This relatively favourable safety profile, however, does not make up for the lack of efficacy: a harmless but ineffective treatment is still not justified. The minimum requirements of donor screening are discussed separately in the literature;816, 817 our own procedure is described below, in the Safety section.

An important distinction

Two meta-analyses from 2023, working from the same narrow literature, reach different conclusions: one found a significant improvement in blood sugar, HOMA-IR, blood pressure and the lipids as well,807 the other found none on HOMA-IR or on body weight.821 The difference arises from the trials included and from the analytical decisions — and this is exactly what shows how small and how sensitive this evidence base is. When the inclusion or exclusion of a few trials reverses the conclusion, the result is not yet solid.

What no provider can responsibly promise. In a metabolic indication, neither weight loss, nor a reduction in the need for medicines, nor a lasting metabolic improvement can be promised. What there are data on is a small, short-lived shift in a few laboratory values — alongside the established treatment, supplementing it. The indication for the treatment and its timing are decided in every case by the treating physician, and diet, exercise and drug treatment must not be abandoned.
The backbone of this page

Point by point — separately for body weight and for metabolism

Below we ask six questions. For each of them we give the answer first for body weight, then for the metabolic markers — in the same breakdown, side by side. This way the difference is visible too, the difference that would be lost in a text that blurred them together.

1. What was actually measured?

Body weight

Kilograms and body mass index. Simple, cheap, objective endpoints that every trial recorded. That is precisely why there is no excuse: if there were an effect, it would be easiest to see on this endpoint.821, 809

Metabolism

Fasting blood sugar, HbA1c, insulin level, HOMA-IR, blood lipids. One study went further than this: it measured insulin sensitivity with the euglycaemic clamp technique, which is the reference method in this field.194, 804

2. What came out?

Body weight

Nothing. For body weight the difference was 2.72 kg (95% CI −4.74 … +10.18), for BMI −0.22 kg/m² (95% CI −1.36 … +0.92) — neither is significant.821 In the 2025 analysis the difference of −0.65 for BMI did not reach the threshold of significance either.809

Metabolism

A small but measurable shift. Fasting blood sugar −0.12 mmol/L, HbA1c −0.37 mmol/mol, insulin −24.77 pmol/L, HDL cholesterol +0.07 mmol/L — all significant, all small. HOMA-IR did not differ.821

3. How reliable is the evidence?

Body weight

A small sample, a result pointing one way. Nine randomised trials, 303 patients; between the trials the scatter on body weight is considerable (I² = 50%). Here, however, the negative result is consistent: there is no analysis that shows weight loss.821, 809

Metabolism

A small sample, a divergent result. Two meta-analyses from 2023 judge the same literature in opposite ways: one finds a significant improvement in HOMA-IR and in the lipids as well,807 the other does not.821 The strength of the evidence is rated low by the authors themselves.809

4. What do the professional guidelines say?

Body weight

There is no recommendation. No obesity treatment guideline lists microbiota transfer among the tools of weight reduction. The guideline toolkit is diet, exercise, behavioural therapy, drug treatment and bariatric surgery.

Metabolism

Here too there is no recommendation. The treatment guidelines for type 2 diabetes and metabolic syndrome do not include the procedure. The research direction is recognised; clinical application is not.

5. Where does the uncertainty lie?

Body weight

In whether we are measuring the right endpoint at all. In the four-year adolescent follow-up the body mass index did not differ, but the waist circumference, the body fat percentage and the inflammatory marker did.808 It may be that the scales are the wrong instrument — but that is a hypothesis, not a result.

Metabolism

In how long it lasts and in patient selection. Beyond twelve weeks the difference disappears,821 and the response depends on the recipient's baseline gut flora.712, 811 We do not know in advance who will respond — nor for how long.

6. What is the alternative — and where does MTT belong?

Body weight

Diet, exercise, behavioural therapy, drug and surgical treatment. The evidence for these is orders of magnitude stronger. On this endpoint microbiota transfer has no place — it is not an alternative, because it does not work.

Metabolism

The established metabolic treatment, supplemented. In the studies there was a result where fibre supplementation or a lifestyle intervention accompanied it.805, 806 MTT is therefore at most supplementary, under medical supervision, after an informed decision.

In summary

AspectBody weightMetabolic markers
What was measured?kilograms, body mass indexblood sugar, HbA1c, insulin, HOMA-IR, blood lipids
What came out?no effecta small but measurable improvement
Reliability9 RCTs, 303 patients; the negative result is consistentthe same sample; the meta-analyses contradict one another
Guidelinesno recommendationno recommendation
Uncertaintythe choice of endpointhow long the effect lasts and who the responders are
Alternativediet, exercise, medication, surgery — cannot be replacedthe established treatment, supplemented
For whom might it come into question?for this endpoint no one — it cannot be promisedwith a confirmed metabolic abnormality, with the agreement of the treating physician
Safety

Safety you can rely on

We went through the safety data measured in the publications above: a large pooled review, follow-up over several years, and the caveat that mild, transient complaints are common. What goes into the capsule, however, does not follow from the literature but from our own procedure.

Donor screening. Every donor goes through our DSQ donor screening framework: bacteriological, virological, parasitological and serological testing, stool testing and a detailed questionnaire.

The window period. A recent infection may not yet be detectable at the moment of donation. That is why we keep the donation frozen, in quarantine: for at least eight weeks, and under no circumstances do we release it until the result of the repeat test after the eighth week has arrived. The repeat test covers those infections that could already have occurred before the donation but became detectable only during the eight weeks.

In every case it is under the guidance of your treating physician that the capsules are to be used.

Scientific background

What you read here is based on

The facts and data on this page come from thirteen publications in all: six randomised controlled trials, three systematic reviews and meta-analyses, a secondary analysis of a randomised trial, a mechanism review and two publications dealing with donor screening.

[194] Vrieze, A., Van Nood, E., Holleman, F. et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome Gastroenterology 2012. doi:10.1053/j.gastro.2012.06.031

PMID 22728514 · randomised, controlled proof-of-concept trial – lean donor, insulin sensitivity

Male recipients with metabolic syndrome were randomized to small-intestinal infusion of allogeneic (lean-donor) or autologous gut microbiota. Six weeks after lean-donor infusion, insulin sensitivity increased (median glucose disappearance rate: 26,2 → 45,3 μmol/kg/min; p<0,05), with parallel increase in butyrate-producing intestinal microbiota. The proof-of-concept study supports development of gut microbiota as a therapeutic agent to improve insulin sensitivity in humans.Source: references-v2.bib · ref-194

[712] Kootte, R., Levin, E., Salojärvi, J., et al. Improvement of Insulin Sensitivity after Lean Donor Feces in Metabolic Syndrome Is Driven by Baseline Intestinal Microbiota Composition Cell metabolism 2017. doi:10.1016/j.cmet.2017.09.008

PMID 28978426 · randomised trial with mechanistic analysis – predictors of who responds

Baseline microbiota composition determines who responds favorably to FMT in metabolic syndrome — Allogenic FMT improved insulin sensitivity at 6 weeks; the effect did not persist at 18 weeks. Response correlates with baseline low microbiota diversity. Plasma metabolites (GABA) changed. Mechanism-revealing follow-up to the Vrieze 2012 trial.Source: references-v2.bib · ref-712

[804] Yu, E., Gao, L., Stastka, P., et al. Fecal microbiota transplantation for the improvement of metabolism in obesity: The FMT-TRIM double-blind placebo-controlled pilot trial PLoS medicine 2020. doi:10.1371/journal.pmed.1003051

PMID 32150549 · randomised, double-blind, placebo-controlled trial (FMT-TRIM) – negative metabolic endpoint

Weekly oral FMT capsules produce durable engraftment in obese individuals, but metabolic parameters do not improve significantly — 24 obese IR patients, 6 weeks of weekly FMT capsules vs. placebo. Engraftment occurred, but insulin sensitivity (euglycemic clamp), HOMA-IR, and body weight did not improve significantly. Negative but important result: engraftment alone is not sufficient.Source: references-v2.bib · ref-804

[805] Mocanu, V., Zhang, Z., Deehan, E., et al. Fecal microbial transplantation and fiber supplementation in patients with severe obesity and metabolic syndrome: a randomized double-blind, placebo-controlled phase 2 trial Nature medicine 2021. doi:10.1038/s41591-021-01399-2

PMID 34226737 · randomised, double-blind trial – microbiota transfer combined with fibre supplementation

FMT + low-fermentation fiber supplementation significantly improves insulin resistance in severe obesity and metabolic syndrome — 70 participants (FMT-HF, FMT-LF, HF, LF groups). FMT+LF group: HOMA2-IR improved significantly after 6 weeks (p=0.02). No improvement in FMT+HF group. Type of fiber supplementation modulates FMT efficacy. No serious adverse events.Source: references-v2.bib · ref-805

[806] Ng, S., Xu, Z., Mak, J., et al. Microbiota engraftment after faecal microbiota transplantation in obese subjects with type 2 diabetes: a 24-week, double-blind, randomised controlled trial Gut 2022. doi:10.1136/gutjnl-2020-323617

PMID 33785557 · randomised trial with 24-week follow-up – engraftment and lipid profile

Repeated FMT + lifestyle intervention produces durable engraftment and lipid-profile improvement in obese type 2 diabetics — 61 obese T2DM patients, 24-week follow-up. Engraftment 100% in FMT+LSI, 88% in FMT, 22% in placebo+LSI (p<0.0001). FMT+LSI: LDL cholesterol and liver stiffness decreased (p<0.05). Lifestyle intervention potentiates the effect of FMT.Source: references-v2.bib · ref-806

[807] Zecheng, L., Donghai, L., Runchuan, G., et al. Fecal microbiota transplantation in obesity metabolism: A meta analysis and systematic review Diabetes research and clinical practice 2023. doi:10.1016/j.diabres.2023.110803

PMID 37356723 · systematic review and meta-analysis – ten randomised trials, 334 patients

FMT significantly improves parameters associated with obesity and metabolic syndrome: blood pressure, glucose, HOMA-IR, lipids, and CRP — Meta-analysis of 10 RCTs, 334 patients. FMT significantly improved fasting glucose, HOMA-IR, systolic/diastolic blood pressure, total cholesterol, HDL, LDL, triglycerides, and CRP. Abdominal adiposity indices were negatively associated. FMT is most effective in obese patients with elevated blood pressure, dysglycemia, and dyslipidemia.Source: references-v2.bib · ref-807

[808] Wilson, B., Zuppi, M., Derraik, J., et al. Long-term health outcomes in adolescents with obesity treated with faecal microbiota transplantation: 4-year follow-up Nature communications 2025. doi:10.1038/s41467-025-62752-4

PMID 40877311 · four-year follow-up of a randomised trial – adolescent obesity

This is the 4-year follow-up of the Gut Bugs trial, a double-blind, randomised, placebo-controlled study of faecal microbiota transplantation (FMT) in adolescents with obesity carried out in New Zealand. Fifty-five of the 87 original participants (27 FMT, 28 placebo) were re-assessed in an unblinded follow-up. Body mass index did not differ between the groups once sex, age, diet and physical activity were taken into account, but FMT recipients had a smaller waist circumference (10.0 cm less), lower total body fat (4.8 percent lower), a more favourable metabolic syndrome severity score (by 0.58), markedly lower systemic inflammation (hs-CRP 68 percent lower) and higher HDL cholesterol (by 0.16 mmol/L). Glucose markers and the remaining lipid parameters showed no group differences. Shotgun metagenomic sequencing revealed long-lasting changes in gut microbiome richness, composition and functional capacity, with donor-derived bacterial and bacteriophage strains still detectable four years on. The authors present FMT as a microbiome-augmenting intervention that deserves further investigation in obesity rather than as an established treatment.Source: references-v2.bib · ref-808

[809] Zhang, Y., Cao, J., Wang, Y., et al. Effects of fecal microbiota transplantation on glycemic and lipid profiles in overweight or obese patients with metabolic disorders: a systematic review and meta-analysis Frontiers in endocrinology 2025. doi:10.3389/fendo.2025.1737543

PMID 41473248 · systematic review and meta-analysis – eleven randomised trials, 320 patients

This is a systematic review and meta-analysis, published in Frontiers in Endocrinology in December 2025, of randomised controlled trials of faecal microbiota transplantation (FMT) in overweight or obese adults with metabolic disease such as type 2 diabetes, metabolic syndrome or fatty liver disease. Eleven trials with 320 participants were pooled with a random-effects model, the primary outcomes being change from baseline in BMI, HOMA-IR and HbA1c. In the primary analysis FMT produced only non-significant trends towards a lower BMI (mean difference -0.65, p = 0.070) and better insulin sensitivity (HOMA-IR mean difference -0.64, p = 0.062), and no effect at all on HbA1c (mean difference 0.06, p = 0.742). The negative result proved fragile: in a sensitivity analysis that assumed a correlation of 0.75 rather than 0.5 when estimating the standard deviation of change, the BMI benefit did become statistically significant (p = 0.010), and meta-regression linked the HbA1c response to the treatment regimen, the length of follow-up and patients' baseline characteristics. The authors rate the certainty of evidence as low and conclude that the true efficacy of FMT in systemic metabolic disorders remains unresolved, largely because administration protocols and donor material are not standardised.Source: references-v2.bib · ref-809

[810] Iqbal, M., Yu, Q., Tang, J., Xiang, J. Unraveling the gut microbiota's role in obesity: key metabolites, microbial species, and therapeutic insights Journal of bacteriology 2025. doi:10.1128/jb.00479-24

PMID 40183584 · review – gut bacteria, metabolites and the mechanism of obesity

This is a review article in the Journal of Bacteriology on the part the gut microbiota plays in obesity. It describes bacteria that appear to favour weight gain, among them Clostridium XIVb, Dorea species, Enterobacter cloacae and Collinsella aerofaciens, which increase the energy harvested from food, raise gut permeability and sustain inflammation by allowing lipopolysaccharide to reach the bloodstream. Against these it sets organisms such as Akkermansia muciniphila and members of the genera Lactobacillus and Bifidobacterium, which strengthen the gut barrier, support short-chain fatty acid production and modulate fasting-induced adipose factor, so that less fat is stored and inflammation is dampened. The short-chain fatty acids acetate, propionate and butyrate act on G-protein coupled receptors to regulate lipid metabolism and to promote the browning of white adipose tissue, which raises heat production and energy expenditure, while lipopolysaccharide pushes metabolism the other way, towards insulin resistance and fat accumulation. The authors see microbiota-directed treatment, including approaches that encourage white fat browning and activate brown adipose tissue, as a promising direction in obesity, but they stress that individual differences in the microbiome call for personalised strategies and that clinical translation still requires further research.Source: references-v2.bib · ref-810

[811] Zhang, Z., Mocanu, V., Deehan, E., et al. Recipient microbiome-related features predicting metabolic improvement following fecal microbiota transplantation in adults with severe obesity and metabolic syndrome: a secondary analysis of a phase 2 clinical trial Gut microbes 2024. doi:10.1080/19490976.2024.2345134

PMID 38685731 · secondary analysis of a randomised trial – who responds to treatment

A secondary analysis of a randomised, placebo-controlled phase 2 trial in adults with severe obesity and metabolic syndrome, asking which characteristics of the recipient decide whether faecal microbiota transplantation followed by dietary fibre supplementation improves insulin resistance. Participants who received FMT from one of four donors together with a fibre supplement were divided into HOMA-IR responders (n = 21) and non-responders (n = 8). Baseline faecal microbiota composition at genus level predicted the improvement in HOMA2-IR at week 6 (ROC-AUC 0.70), and Prevotella stood out as an important predictor, with responders carrying significantly lower relative abundance than non-responders (p = 0.02). Responders also gained more bacterial richness (Chao1) after the transplant and showed more consistent engraftment of donor-specific amplicon sequence variants, among them Faecalibacillus intestinalis, Roseburia species and Christensenellaceae species. Engraftment itself was tied closely to the recipient's starting state, including gut microbial diversity, fibre and nutrient intake, inflammatory markers and bile acid derivative levels. The authors read this as an argument for precision microbial therapy matched to the individual recipient rather than a one-size-fits-all transplant protocol.Source: references-v2.bib · ref-811

[816] Kassam, Z., Dubois, N., Ramakrishna, B. et al. Donor Screening for Fecal Microbiota Transplantation N Engl J Med 2019. doi:10.1056/NEJMc1913670

PMID 31665572 · requirements for donor screening

Kassam and colleagues' 2019 New England Journal of Medicine correspondence on 'Donor Screening for Fecal Microbiota Transplantation' was written in the wake of an FDA safety alert reporting two cases of extended-spectrum beta-lactamase (ESBL)-producing E. coli bacteremia — one fatal — transmitted via FMT from a donor not screened for MDROs. The OpenBiome team, the leading US stool bank, summarises updated donor-screening protocols, including ESBL/CRE PCR and culture, and discuss broader implications for biosafety, donor recruitment, and stool-bank operations. The letter directly informed updated FDA, ESCMID and EBP donor-screening recommendations and is the canonical citation for AMR-driven screening intensification.Source: references-v2.bib · ref-816

[817] Rondinella, D., Quaranta, G., Rozera, T., et al. Donor screening for fecal microbiota transplantation with a direct stool testing-based strategy: a prospective cohort study Microbes and infection 2024. doi:10.1016/j.micinf.2024.105341

PMID 38679228 · prospective cohort – donor screening based on direct stool testing

Direct stool identity testing-based donor screening strategy — Of 277 donations, 99 (36%) were discarded due to pathogen positivity (most common: EPEC n=37, Blastocystis n=20). Among 337 approved aliquots used in FMT: no serious adverse events occurred over 12 weeks.Source: references-v2.bib · ref-817

[821] Qiu, B., Liang, J., Li, C. Effects of fecal microbiota transplantation in metabolic syndrome: A meta-analysis of randomized controlled trials PLOS ONE 2023. doi:10.1371/journal.pone.0288718

systematic review and meta-analysis – nine randomised trials, 303 patients

Pooled analysis of nine randomised trials and 303 participants: no significant effect on body weight or BMI; a few metabolic markers improve slightly, but beyond twelve weeks there is no difference. — In the short-term analysis, weight (MD 2.72 kg; 95% CI −4.74 … +10.18) and BMI (MD −0.22 kg/m²; 95% CI −1.36 … +0.92) did not differ from control. Fasting blood glucose (MD −0.12 mmol/L; 95% CI −0.23 … −0.01), HbA1c (MD −0.37 mmol/mol; 95% CI −0.73 … −0.01), insulin (MD −24.77 pmol/L; 95% CI −37.60 … −11.94) and HDL cholesterol (MD +0.07 mmol/L; 95% CI +0.02 … +0.11) improved significantly but by small margins; HOMA-IR did not. In follow-up beyond twelve weeks the authors found no difference between the groups on any endpoint. No serious adverse effects were reported; the authors position the procedure as adjunctive therapy.Source: references-v2.bib · ref-821

So what is the next step?

If you want to find out whether your case is suitable, when things happen and what it costs, you will find that on the service page.

Obesity and metabolism — the service →

The MicroBiome Bank service is not a substitute for professional medical advice, diagnosis or treatment. The decision to use it rests in every case with the treating physician.