How Does the Gut Microbiome Influence Healthy Ageing?

The gut microbiome changes with age and can influence health

The microbiome does more than respond to what happens inside the body. It provides an important link between environmental influences and the body.

Diet, lifestyle and environmental exposures can influence the microbiome. In turn, microorganisms and their products interact with the body and can affect immune, metabolic and neurological functions.

The relationship works in both directions. The microbiome changes as the body ages, while microbiome-related signals can also influence age-related decline and disease risk.

Age is only one factor shaping the microbiome

Changes observed in older people cannot be attributed to chronological age alone.

Progressive physiological changes associated with ageing can alter the intestinal environment. Diet, medications, reduced physical activity and reduced social contact can also contribute.

This makes the microbiome of an older person the result of multiple interacting influences rather than age alone.

Ageing-related and disease-related changes overlap — but are not the same

This is one of the central conclusions of the review.

Some microbial changes occur with increasing age and are also associated with poorer health. Other changes associated with ageing are not characteristic of unhealthy ageing.

The authors identified different groups of microorganisms showing distinct patterns. Some decreased with age and were associated with healthier ageing. Some increased with age and were associated with unhealthy ageing. Others increased with age but were depleted in people experiencing unhealthy ageing.

Age-related microbiome change therefore should not automatically be interpreted as microbiome deterioration.

Microbiome function matters as well as composition

The authors considered both compositional and functional changes in the microbiome.

The potential influence of the microbiome on ageing does not depend only on which microorganisms are present.

Microorganisms produce and transform many substances that interact with human physiology. These include short-chain fatty acids, amino acid metabolites, bile acids and other compounds.

Through these substances, the microbiome can influence metabolism, inflammation, immune responses and communication with other organs.

Understanding the ageing microbiome therefore requires looking beyond a simple list of bacterial species.

The microbiome could potentially become a target for healthier ageing

The authors examined whether microbiome changes associated with unhealthy ageing could potentially be modified.

Human studies have investigated several approaches. These include dietary interventions, prebiotics, probiotics and combinations of microorganisms with prebiotics. Other approaches include postbiotics and faecal microbiota transplantation.

The outcomes studied have also varied. Some interventions have reported changes in inflammation, insulin resistance, frailty, cognitive function and other measures of health. Results have not been consistent across all interventions or outcomes.

Diet is particularly relevant because it can influence the composition and function of the microbiome. Beneficial responses to microbiome-related dietary interventions have been observed. However, the response can differ substantially between individuals.

One reason is the microbiome present before an intervention begins. The same dietary intervention may not produce the same response in two people with different baseline microbiomes.

The authors therefore propose that future strategies may need to become more personalized. Some people may respond to dietary changes alone. Others may eventually require a combination of dietary intervention and targeted restoration of microorganisms that have been lost.

The evidence is still limited.

Only five of the intervention studies discussed in the review included more than 100 participants. Excluding a meta-analysis and very small faecal microbiota transplantation reports, the average size of the remaining intervention studies in older people was approximately 36 participants. Many studies also used relatively low-resolution methods for analyzing the microbiome.

The authors therefore describe microbiome-based interventions to promote healthy ageing in older people as a work in progress.

The gut microbiome provides an important biological connection between the body, diet, lifestyle and the environment.

This is particularly relevant to longevity because the microbiome is not fixed. It changes throughout life and responds to factors such as diet, medications, health and lifestyle.

Healthy ageing cannot be reduced to having more or less of one particular bacterium. Changes in the microbiome are complex. Some are associated with poorer health, while others may occur in people ageing in good health.

The function of the microbiome also matters. Microorganisms can produce substances that interact with metabolism, inflammation, immune function and other biological processes.

Another important feature is that the microbiome can be modified.

Diet is one way of influencing the gut microbial environment. Prebiotics, probiotics and other microbiome-directed approaches are also being investigated.

But changing the microbiome does not automatically mean improving health. The effect of an intervention can depend on the microbiome present before treatment and on characteristics of the individual.

This creates an important direction for longevity medicine: moving from general microbiome interventions towards a better understanding of which intervention may be useful for which person.

The gut microbiome is increasingly measurable in considerable detail. Modern methods can identify microorganisms present in the gut and provide information about the genes and potential functions represented within the microbial community.

The clinical challenge is interpreting what an individual microbiome profile means for a particular person.

There is substantial natural variation between people. Diet, medications, age, lifestyle, health and environment can all influence the microbiome. There is also no single universal microbiome configuration that defines health for everyone.

This means that an individual microbiome result should not be reduced to a list of bacteria that are simply classified as good, bad, too high or too low.

The response to an intervention can also depend on the microbiome that is already present. The review describes evidence that responses to dietary interventions can be highly individualized and influenced by baseline microbiome composition.

This has important implications for personalized prevention.

Microbiome information may become more useful when considered together with diet, medications, metabolic health, lifestyle and other clinical information. It may also help identify why the same dietary or microbiome-directed intervention does not produce the same response in every person.

The aim is therefore not simply to measure the microbiome or to change it. The more clinically useful goal is to determine which microbiome findings matter for an individual and which interventions are most appropriate for that person.

This remains an active area of research. The review concludes that convincing evidence for microbiome-based therapies in humans is still limited, while also identifying healthy ageing as an important area in which more precise microbiome-directed strategies could be developed.