Scientific background · Immunosenescence and longevity

What microbiota transfer in ageing is based on — and what it is not based on

This page is the reference background for the immunosenescence and longevity page. It goes through eight publications, in two columns: separately what has been observed, and separately what can be inferred from it. The gap between the two is what this page is about.

What we know today, and what we do not

Short answer. In healthy older people, with an ageing or immunosenescence endpoint, no randomised human trial is available. The human data are cross-sectional observations, which show association; the results showing causation come from animal experiments. That is why this field today is a research direction, not a treatment indication.

What this literature does support

That the gut flora of the ageing organism is different is well documented. The microbiome of centenarians is enriched in bacteria that produce distinctive secondary bile acids — among them isoallolithocholic acid, whose biosynthesis had not previously been described. This compound exerted a strong antimicrobial effect against Gram-positive multidrug-resistant pathogens, including Clostridioides difficile and Enterococcus faecium.815 This is a real observation, and one that makes sense at the level of mechanism.

In the gut flora of elite athletes, higher microbial diversity, more active amino acid synthesis and greater production of short-chain fatty acids can be measured,813 and in a randomised dietary trial the more stable gut flora went together with better endurance performance.814 The relationship between training and the gut flora is two-way, with several described mechanisms.812

In animal experiments causation is visible as well: in old recipients, the microbiota of young donor mice reversed the ageing-related changes in peripheral and brain immunity and in the hippocampal metabolome and transcriptome, and moderated the age-related cognitive and behavioural decline.823 The 2025 review cites similar animal experiments for physical performance, for sarcopenia and for haematopoietic stem cells as well.822

What it does not support

Human efficacy on an ageing endpoint: none. According to the 2025 review, the human clinical evidence still comes primarily from gastrointestinal and certain neurological conditions, not from healthy older people; the authors conclude that the procedure is promising, but that “its full viability and efficacy are still under investigation”, and that it requires further development and optimisation.822 We ourselves have not found a randomised trial that measured an ageing endpoint in healthy older people.

The effect in the animal experiment was selective. In the mouse study the improvement did not extend to every behavioural indicator examined.823 This is an important detail: even in mice it is not a matter of “rejuvenation”, but of the reversal of certain indicators. In ageing research, moreover, inference from rodent to human has a particularly poor record.

Nor is there a validated endpoint. There is no accepted laboratory value that would measure “an improvement in immunosenescence”. Anyone who demonstrates the effect with a “biological age” measure is claiming something for which there is no validated instrument.

Safety

The safety profile of the intervention is known from other indications: mild, transient gastrointestinal complaints are common, a serious event is rare. In the ageing application, however, the other side of the scales is empty: without a proven benefit every risk is harder to defend. That is why we exclude immunosuppression, active oncological treatment and the state following organ transplantation. 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

The justification for selecting the donor and proof of the effect are two different things. That we select a donor with a stable, diverse, well-documented flora is a sensible professional decision. That transferring this flora would improve the recipient's performance capacity or immune status is not proven in humans. The longevity market regularly blurs these two things together; this page does not.

What no provider can responsibly promise. For an ageing purpose, neither life extension, nor the reversal of immunosenescence, nor a “younger biological age” can be promised. What can responsibly be recommended is diet, fibre intake, exercise, sleep and stress management — the effect of these on the gut flora is supported by human data. The place of microbiota transfer within this frame is individual medical judgement, expressly experimental in character.
The backbone of this page

What we have observed — and what follows from it

Below we go through six topics. For each we first describe what has actually been observed, and then, separately, what can be inferred from it — and what cannot. The gap between the two is the real state of this field.

1. The gut flora of centenarians

Observation

A distinctive bile acid metabolism. The microbiome of people who reach a hundred is enriched in bacteria that produce previously undescribed secondary bile acids; isoallolithocholic acid has a strong antimicrobial effect against Gram-positive multidrug-resistant pathogens.815

What follows

That it is worth researching — not that it can be transplanted. This is a cross-sectional observation: someone who has lived a hundred years also has different genetics, a different diet and different medication. Whether the flora is the cause of the long life or its companion cannot be decided from this.

2. The gut flora of elite athletes

Observation

Greater diversity, a different metabolite profile. In elite athletes, higher microbial diversity, more active amino acid synthesis and more short-chain fatty acids can be measured;813 and what goes together with endurance is the stability of the flora, not a single species.814

What follows

The justification for selecting the donor — not proof of the effect. Choosing a donor with a stable, diverse flora is reasonable. But that transferring it would improve the recipient's performance is not proven in humans. Exercise, diet and the flora move together.812

3. The young donor — old recipient experiment

Observation

Causation in mice. In old recipients, the microbiota of young donor mice reversed the ageing-related changes in peripheral and brain immunity, in the hippocampal metabolome and transcriptome, and moderated the age-related behavioural decline.823

What follows

That the effect is possible — not that it occurs in humans. Even in mice the improvement was selective: it did not extend to every indicator. In ageing research, inference from rodent to human fails particularly often. It is precisely this step that is missing.822

4. Lifestyle interventions

Observation

Diet and exercise measurably shape the flora. The effect of fibre intake, fermented foods and regular exercise on the composition and the metabolites of the gut flora is supported by human data, and the effect is two-way.812, 813, 814

What follows

That today this is the only route that can responsibly be recommended. It is cheap, available, and its evidence is orders of magnitude stronger than that of the capsule. That is why we start here, and that is why the course does not replace it.

5. Safety

Observation

A profile known from other indications. Mild, transient gastrointestinal complaints are common, a serious event is rare. The minimum requirements of donor screening are discussed separately in the literature.816, 817

What follows

That with a healthy-person goal the standard is stricter. In disease the risk stands against a proven benefit; here there is nothing to set against it. That is why we exclude immunosuppression, active oncological treatment and the state following organ transplantation.

6. What is missing for proof?

Observation

There is no randomised human trial with an ageing endpoint, and there is no validated measure either with which an improvement in immunosenescence could be demonstrated.822

What follows

That what we do today is a weighing-up, not a treatment. The missing trial is placebo-controlled, with a pre-registered endpoint, with healthy older participants and with a long enough follow-up. Until that exists, the responsible position is to state the limitation.

In summary

QuestionWhat we have observedWhat follows from it
Centenariansdistinctive secondary bile acids, with an antimicrobial effectworth researching; causation not proven
Elite athletesgreater diversity, a more stable florathe justification for selecting the donor, not for the effect
Animal experimentyoung flora reverses immune and brain changesthe effect is possible — not proven in humans
Lifestylediet and exercise measurably shape the floratoday this is the only route that can responsibly be recommended
Safetymild complaints are common, a serious event is rarewithout a proven benefit the standard is stricter
Evidenceno randomised human trial, no validated endpointa weighing-up, not a treatment
For whom might it come into question?for this purpose no result can be promised to anyonein the case of an informed decision made jointly with 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 eight publications in all: two human observational studies, one randomised dietary trial, one experimental mouse model, two reviews and two publications dealing with donor screening. There is no randomised human trial with an ageing endpoint among them, because none has been carried out.

[812] Zhao, Z., Zhao, S., Li, W., et al. Gut Microbiota and Exercise-Induced Fatigue: A Narrative Review of Mechanisms, Nutritional Interventions, and Future Directions Nutrients 2026. doi:10.3390/nu18030502

PMID 41683324 · review – gut microbiota, exercise-induced fatigue and athletic performance

The gut microbiome modulates exercise-induced fatigue and athletic performance via metabolic, immunological, and gut-brain axis mechanisms — High-intensity exercise ↑gut permeability, ↓beneficial microbiota; 4 microbiota-mediated pathways identified (energy, redox, barrier, gut-brain); proposes FMT as a future causal validation method (Nutrients, 2026).Source: references-v2.bib · ref-812

[813] Clauss, M., Gérard, P., Mosca, A., Leclerc, M. Interplay Between Exercise and Gut Microbiome in the Context of Human Health and Performance Frontiers in nutrition 2021. doi:10.3389/fnut.2021.637010

PMID 34179053 · review – the two-way relationship between exercise and the gut microbiome

Exercise and the gut microbiome have a bidirectional relationship; elite athletes are characterized by higher microbial diversity and SCFA production, which also affects athletic performance — Elite athletes show high microbial diversity, amino acid synthesis, and SCFA production (propionate, butyrate); moderate exercise reduces inflammation and improves gut barrier; microbiota in turn affects exercise performance — bidirectional axis confirmed (Front Nutr, 2021).Source: references-v2.bib · ref-813

[814] Furber, M., Young, G., Holt, G., et al. Gut Microbial Stability is Associated with Greater Endurance Performance in Athletes Undertaking Dietary Periodization mSystems 2022. doi:10.1128/msystems.00129-22

PMID 35579384 · randomised dietary trial – gut microbial stability and endurance performance

A stable gut microbiome is associated with better endurance performance; a carbohydrate-rich diet is associated with +6.5% performance gain and favorable microbiota change — High-carbohydrate diet: +6.5% running performance (p<0.03) and increase in Prevotella/Bifidobacterium; high-protein: −23.3% performance and reduced microbiota diversity; more stable microbiome — better performance (RCT, mSystems 2022).Source: references-v2.bib · ref-814

[815] Sato, Y., Atarashi, K., Plichta, D. R., et al. Novel bile acid biosynthetic pathways are enriched in the microbiome of centenarians Nature 2021. doi:10.1038/s41586-021-03832-5

PMID 34325466 · human observational study – bile acid metabolism in centenarians

Centenarians display reduced susceptibility to age-related diseases. The authors found that centenarian gut microbiomes are enriched in microorganisms producing unique secondary bile acids, including iso-, 3-oxo-, allo-, 3-oxoallo- and isoallolithocholic acid (isoalloLCA), whose biosynthetic pathway had not been previously described. Screening 68 bacterial isolates from a centenarian's microbiota identified Odoribacteraceae strains as effective producers of isoalloLCA in vitro and in vivo, with 5α-reductase (5AR) and 3β-hydroxysteroid dehydrogenase (3β-HSDH) as the responsible enzymes. IsoalloLCA exerted potent antimicrobial activity against Gram-positive multidrug-resistant pathogens including Clostridioides difficile and Enterococcus faecium. The findings identify a microbiome-derived bile acid axis linked to healthy longevity and a candidate strategy against MDR Gram-positive pathogens.Source: references-v2.bib · ref-815

[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

[822] Borrego-Ruiz, A., Borrego, J. J. Fecal Microbiota Transplantation in Healthy Aging: Challenges and Prospects in Personalized Medicine Journal of Molecular and Clinical Medicine 2025. doi:10.31083/JMCM40022

review – faecal microbiota transplantation and healthy ageing

Review of faecal microbiota transplantation and healthy ageing: the animal findings are encouraging, but there is no human evidence for ageing endpoints. — The authors report that in animals, microbiota from young donors transferred into aged recipients restores the donor-type gut flora; the experiments cited include improved physical fitness, attenuated sarcopenia, improved cognitive measures and rejuvenated haematopoietic stem cells. Human clinical evidence, by contrast, still comes mainly from gastrointestinal and selected neurological conditions, not from healthy older adults. The conclusion is that the procedure shows promise as a microbial approach to ageing-related effects, but its full viability and effectiveness are still under investigation and require further development and optimisation.Source: references-v2.bib · ref-822

[823] Boehme, M., Guzzetta, K. E., Bastiaanssen, T. F. S. et al., Cryan, J. F. Microbiota from young mice counteracts selective age-associated behavioral deficits Nature Aging 2021. doi:10.1038/s43587-021-00093-9

PMID 37117767 · experimental mouse model – microbiota from young donors into aged recipients

Mouse experiment: gut microbiota from young donors reversed age-associated immune and brain changes in aged mice and attenuated part of the behavioural decline. — Faecal microbiota from young (3–4 months) or old (19–20 months) donor mice was transplanted into aged (19–20 months) recipients. Microbiota from young donors reversed ageing-associated differences in peripheral and brain immunity and in the hippocampal metabolome and transcriptome, and attenuated age-associated impairments in cognitive behaviour. The effect was selective, however: it did not extend to every behavioural measure examined. This is an animal study and does not translate directly to humans.Source: references-v2.bib · ref-823

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.

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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.