IPM Take
Exercise rehabilitation already works.
The new question is whether the gut microbiome can help explain why some patients respond better than others, and eventually whether it can be used to personalise rehabilitation.
A review published in npj Biofilms and Microbiomes argues that exercise-induced changes in gut microbial communities and metabolites could become part of a broader model the authors call “intestinal rehabilitation”. Their proposal combines structured exercise with dietary and potentially microbiome-targeted interventions, particularly for people with obesity, diabetes, metabolic disease or limited capacity to exercise.
The idea is scientifically attractive.
Exercise has been associated with increased microbial diversity, short-chain fatty acid-producing bacteria and changes in pathways linked to inflammation, glucose metabolism and cardiovascular function. Small clinical studies have also reported microbiome changes during exercise rehabilitation in patients with coronary disease.
But there is a large gap between detecting a microbial change and knowing that manipulating it improves recovery.
The new review itself acknowledges that human evidence is heterogeneous, much of the mechanistic evidence comes from animal studies, confounding from diet is difficult to remove, and patients with chronic disease or mobility limitations remain underrepresented.
That makes this an important research signal, not a justification for routine microbiome testing, probiotic prescribing or reimbursement.
The policy challenge is familiar: microbiome science is generating biomarkers and commercial possibilities faster than clinical pathways can establish what is actionable.
Executive Summary
Researchers led by Dan Zhong and colleagues reviewed evidence linking exercise rehabilitation with the gut microbiome and proposed a personalised “intestinal rehabilitation” framework. The review was published in npj Biofilms and Microbiomes on 26 September 2026.
The authors describe evidence that endurance and aerobic exercise can alter microbial diversity and the abundance of bacteria involved in producing short-chain fatty acids, while very intense exercise may transiently impair gut barrier function in some settings.
They propose combining exercise with diet and potentially microbiome-targeted interventions and monitoring candidate biomarkers such as microbial diversity, Akkermansia muciniphila, short-chain fatty acids, trimethylamine N-oxide, inflammatory markers and measures of intestinal barrier integrity.
However, these markers are proposed candidates, not validated clinical tools for rehabilitation decision-making.
The strongest translation problem remains causality.
A 2025 randomised study in sedentary adults with overweight or obesity found that a combined energy-restriction and vigorous-exercise intervention improved metabolic health and altered the microbiome, but because diet and exercise changed together, the study could not isolate the microbiome as the mechanism producing those health benefits.
In cardiovascular rehabilitation, a small study of 60 patients after percutaneous coronary intervention found differences in gut microbes and metabolites between high-intensity interval and moderate continuous exercise groups alongside improvements in exercise performance. The findings support further investigation but do not establish that microbial changes caused the functional improvement.
Why it matters
- HTA bodies: A future microbiome-guided rehabilitation programme would need to demonstrate added clinical value over established exercise rehabilitation, not simply show changes in microbial composition. Standardised testing, reproducibility, meaningful endpoints and evidence that altering the microbiome improves patient outcomes would all be required.
- Payers: Microbiome sequencing, biomarker panels, probiotics and personalised nutrition could add considerable cost to rehabilitation. Without evidence that they improve recovery, reduce hospitalisation or increase adherence beyond conventional programmes, reimbursement would be premature.
- Industry / innovation partners: The rehabilitation microbiome creates opportunities for diagnostics, digital monitoring, nutrition platforms and microbiome-targeted products. It also creates substantial overclaiming risk. Association between a bacterial species and recovery is not evidence that adding that organism, eliminating another or selling a microbiome test improves outcomes.
Exercise rehabilitation has traditionally been built around a visible system.
The heart pumps better. Muscles become stronger. Walking distance increases. Glucose control improves.
Now researchers are asking whether another system, hidden inside the gastrointestinal tract, contributes to those changes.
The gut contains a vast microbial ecosystem capable of producing metabolites that influence immune signalling, metabolism and intestinal barrier function. The new npj Biofilms and Microbiomes review examines whether exercise-induced changes in this ecosystem could partly mediate the benefits seen during rehabilitation.
The answer so far is intriguing.
It is also incomplete.
Exercise changes the microbiome
Across observational and interventional studies, physical activity has been associated with changes in gut microbial composition.
Endurance activities including running, swimming and cycling have been linked with greater microbial diversity and changes in bacteria involved in carbohydrate metabolism and production of short-chain fatty acids. Moderate to vigorous aerobic activity has also been associated with greater abundance of organisms such as Akkermansia and Bifidobacterium in some studies.
Short-chain fatty acids are particularly interesting because they can influence intestinal barrier integrity, immune function and metabolic signalling.
That provides a plausible pathway linking the gut to obesity, insulin resistance and cardiovascular disease.
But microbial responses to exercise are not universal.
A separate 2026 review of human and animal evidence concluded that responses vary considerably between individuals and that human randomised evidence remains limited. It also noted that exercise intensity, baseline microbiota, diet and training status can all influence results.
The microbiome is therefore not responding to exercise in isolation.
It is responding to a person.
Cardiac rehabilitation provides an early test case
The hypothesis becomes especially interesting in cardiovascular rehabilitation.
A prospective study involving 60 people with coronary heart disease after PCI compared high-intensity interval training with moderate continuous exercise over 12 weeks.
The high-intensity group achieved greater improvement in six-minute walk performance, while both groups improved LDL cholesterol and peak oxygen uptake.
Researchers also identified 29 microbial species and 30 plasma metabolites that differed between the groups, with several associated with functional performance.
That is exactly the type of result that makes microbiome research attractive.
It is also exactly where caution is needed.
Finding that better exercise performance occurs alongside different microbial profiles does not show that those microbes produced the improvement. Training itself could independently change cardiovascular function and microbial composition.
Diet, medication and baseline disease can complicate the picture further.
The result generates a mechanism to investigate.
It does not create a new rehabilitation treatment.
What is “intestinal rehabilitation”?
Zhong and colleagues go one step further by proposing intestinal rehabilitation as a conceptual framework.
For people capable of exercise, it could involve structured training together with diets designed to support microbial diversity and beneficial metabolite production.
For patients with restricted mobility, including frail older adults and people with advanced cardiac, pulmonary or neurological disease, the authors suggest that dietary or microbiome-targeted strategies might eventually help mitigate dysbiosis while physical capacity is limited.
The framework also proposes a broad monitoring system.
Potential measures include microbial alpha and beta diversity, abundance of Akkermansia muciniphila, circulating or faecal short-chain fatty acids, TMAO, tryptophan metabolites, inflammatory biomarkers and measures associated with gut barrier function.
The sophistication of that list illustrates both the opportunity and the problem.
There is currently no clinically established microbiome panel telling a rehabilitation team that one patient needs more aerobic exercise, another needs a probiotic and a third needs a particular dietary intervention.
The proposed biomarkers require validation before they can guide care.
Current rehabilitation policy is much further ahead on exercise than microbiomics
The contrast with established cardiac rehabilitation is striking.
The first dedicated ESC Guidelines on cardiac rehabilitation, released in August 2026, provide detailed recommendations on exercise prescription, risk assessment, programme structure, patient-centred goals, psychosocial support and delivery models.
Microbiome-guided rehabilitation is not part of that framework.
A search of the guideline finds no reference to the microbiome.
That does not mean the emerging science is irrelevant.
It shows how far it still has to travel before becoming policy.
A rehabilitation intervention needs more than mechanistic plausibility. Health systems need to know whether it changes outcomes patients care about, whether clinicians can interpret the result reliably, whether the intervention works across populations and whether the additional cost provides value.
The commercial temptation may arrive early
Microbiome science has another complication.
It can be monetised before it is clinically mature.
Consumer microbiome sequencing, probiotics, personalised nutrition products and metabolite testing already create a commercial ecosystem in which mechanistic research can quickly be translated into health claims.
The intestinal-rehabilitation concept could accelerate that interest.
But the review itself does not establish that commercially available microbiome testing improves rehabilitation, nor does it demonstrate that probiotics broadly improve recovery. In fact, the authors explicitly note that probiotic effects are not universal and that interventions would need to be individualised.
That distinction should matter to regulators and payers.
A microbial signature can be biologically interesting without being clinically actionable.
The evidence gap is now the story
The strongest conclusion of the review may therefore be its list of unanswered questions.
Most existing studies involve healthy or physically active participants rather than the patients most likely to need rehabilitation.
Study methods vary widely.
Exercise effects are difficult to separate from dietary changes.
Observational associations dominate many parts of the literature.
And long-term safety and effectiveness of microbiome-targeted interventions remain uncertain.
Those are not minor methodological problems.
They determine whether intestinal rehabilitation becomes a genuine precision-medicine strategy or simply another attractive microbiome hypothesis.
The next step should therefore not be routine sequencing of rehabilitation patients.
It should be better trials.
Those trials need to test whether microbiome changes mediate recovery, whether modifying those changes improves meaningful clinical outcomes and whether microbiome-guided care outperforms rehabilitation programmes already known to work.
Exercise has already earned its place in cardiometabolic medicine.
The microbiome has not yet earned a place beside the exercise prescription. But researchers are beginning to define what evidence it would need to get there.
