The Microbiome and Its Role in Health and Longevity

For a long time, the gut was regarded primarily as a digestive organ. Today, it is clear that it does far more than absorb nutrients. Trillions of microorganisms live in the human gut and together form the gut microbiome. This complex ecosystem influences metabolism, the immune system, the integrity of the intestinal barrier and even communication between the gut and the brain. Over the past two decades, the microbiome has therefore developed into one of the most dynamic fields of medical research.

Interest in intestinal microorganisms is growing particularly in longevity research. Observational studies show that people with an exceptionally high life expectancy often display characteristic changes in their microbiome. At the same time, disturbances in microbial composition are associated with numerous age-related diseases, including cardiovascular disease, type 2 diabetes, obesity, chronic inflammatory bowel disease and neurodegenerative disorders.

The microbiome is not an independent cause of healthy or unhealthy ageing. Rather, it influences a wide range of biological processes that collectively determine how resilient the organism remains to ageing processes. Its particular significance lies in the fact that, unlike many genetic factors, it can be influenced at least partly through nutrition, lifestyle and certain medical interventions.

But what exactly is meant by the microbiome? Which functions do gut bacteria perform for the human body? And what does current research reveal about their influence on health and longevity?

What is the microbiome?

The term microbiome describes the totality of all microorganisms and their genetic information within a particular habitat. In the human body, bacteria, archaea, viruses and fungi colonise almost every surface, including the skin, oral cavity, respiratory tract and urogenital tract.

The largest proportion, however, is found in the gut microbiome. The large intestine alone contains several hundred different bacterial species, with a total of approximately 10¹³ to 10¹⁴ microorganisms. Their genetic diversity exceeds that of the human genome many times over.

Although people often speak of “good” or “bad” gut bacteria, this classification is too simplistic. Many microorganisms perform different functions depending on the composition of the community and environmental conditions. What matters less, therefore, is the presence of individual species than the stability and functional diversity of the entire microbial ecosystem.

How does the gut microbiome develop?

The microbiome is not a static system. Its composition changes throughout life.

Initial colonisation begins around the time of birth. Factors such as mode of delivery, breastfeeding, the use of antibiotics during the first years of life and environmental exposure strongly influence which microorganisms become established first.

During the first three years of life, an increasingly stable microbial ecosystem develops. In adulthood, the microbiome remains comparatively stable, but it continues to respond to nutrition, medication, infections, exercise, sleep and other lifestyle factors.

As age increases, bacterial composition changes again. Diversity, meaning the variety of different microorganisms, often declines. At the same time, pro-inflammatory bacterial species may increase, while beneficial producers of short-chain fatty acids decline.

However, these changes are not caused exclusively by biological ageing. Diseases, medications, reduced physical activity and changes in diet also contribute.

Why diversity is a hallmark of a healthy microbiome

A central feature of a healthy gut microbiome is its diversity, meaning the variety of different microorganisms.

High diversity does not necessarily mean that as many bacterial species as possible must be present. Functional diversity is much more important. Different microorganisms perform different metabolic tasks and complement one another.

A diverse microbiome offers several advantages:

• Nutrients can be utilised more efficiently.
• Pathogens find fewer unoccupied ecological niches.
• Metabolic products are generated in more balanced quantities.
• The immune system is regulated in a more differentiated way.
• The ecosystem responds more resiliently to disturbances.

This principle resembles natural ecosystems. A species-rich forest can often compensate for storms, drought or pest infestation more effectively than a monoculture. The gut microbiome also benefits from biological diversity.

Which functions does the microbiome perform?

For a long time, it was assumed that gut bacteria merely supported the digestion of indigestible food components. In fact, their influence extends much further.

Supporting digestion

The human body does not possess the enzymes required to break down many plant-based fibres completely.

Gut bacteria perform this task. They ferment indigestible carbohydrates and produce various metabolic products that in turn benefit the human body.

The so-called short-chain fatty acids are particularly important:

• butyrate
• acetate
• propionate

They serve as an energy source for the cells of the intestinal mucosa and also influence numerous metabolic processes throughout the body.

Production of bioactive molecules

The microbiome produces a wide range of biologically active substances.

These include:

• short-chain fatty acids
• secondary bile acids
• various vitamins, including vitamin K and several B vitamins
• neurotransmitters or their precursors
• metabolites derived from amino acids and polyphenols

These molecules act not only locally in the gut but can also enter the bloodstream and influence metabolism and the function of various tissues in other organs.

Protection against pathogens

A healthy microbiome makes it more difficult for potentially harmful microorganisms to become established.

Existing bacteria compete for nutrients and attachment sites on the intestinal wall. At the same time, many species produce antimicrobial substances that inhibit the growth of other microbes.

This mechanism is known as colonisation resistance and is an important component of the body’s natural defence system.

Regulation of the immune system

Approximately seventy percent of the body’s immune cells are located in the gut.

There is therefore a constant exchange of information between gut bacteria and immune cells.

The microbiome helps to:

• control the development of different immune-cell types,
• limit excessive immune reactions,
• promote the formation of regulatory T cells,
• control inflammatory processes.

A balanced microbial composition therefore supports the balance between effective immune defence and controlled immune regulation.

The intestinal barrier as the interface between the microbiome and the body

The intestinal mucosa forms the body’s largest interface with the outside world.

It performs a demanding task: on the one hand, it must absorb nutrients efficiently. On the other, it must prevent bacteria, toxins and undigested food components from entering the bloodstream uncontrollably.

This barrier consists of several components. These include the mucus layer, specialised epithelial cells, so-called tight junctions between the cells and numerous immune cells.

The microbiome makes a major contribution to maintaining this barrier. Butyrate in particular supports the energy supply of intestinal epithelial cells, strengthens the tight junctions and promotes regeneration of the intestinal mucosa.

If microbial composition becomes disturbed, the barrier function can be impaired. This allows increased amounts of bacterial components such as lipopolysaccharides to enter the bloodstream. This process is associated with chronic inflammatory reactions and various metabolic diseases.

Short-chain fatty acids: small molecules with major effects

Among the most important metabolic products of the gut microbiome are the short-chain fatty acids (Short Chain Fatty Acids, SCFAs). They are produced when gut bacteria ferment fibre that the human body cannot digest on its own.

The three most important representatives are:

• butyrate
• acetate
• propionate

For a long time, these molecules were viewed primarily as an energy source for the intestinal mucosa. Today, it is known that their effects extend much further.

Butyrate protects the intestinal mucosa

Butyrate is the main energy source for epithelial cells in the large intestine. An adequate supply supports regeneration of the intestinal mucosa and strengthens barrier function.

Butyrate also influences various signalling pathways in the immune system. It promotes the formation of regulatory T cells, inhibits excessive inflammatory reactions and helps balance the immune response in the gut.

Butyrate also has interesting molecular properties. Among other effects, it acts as an inhibitor of certain histone deacetylases. This changes the activity of individual genes without altering the DNA itself. This epigenetic mechanism is one of the most intensively studied interfaces between nutrition, the microbiome and health.

Acetate and propionate act throughout the body

Acetate is the most abundant short-chain fatty acid. After it is produced, it enters various tissues through the bloodstream and serves there as a substrate for different metabolic processes.

Propionate is taken up primarily by the liver. Among other effects, it influences glucose homeostasis and various signalling pathways involved in energy metabolism.

All three fatty acids also activate specific receptors on immune cells and metabolic tissues. In this way, they influence inflammatory processes, fat metabolism and insulin sensitivity.

The microbiome and metabolism

The gut microbiome is in close communication with human metabolism. Its metabolic products influence nutrient absorption and utilisation, energy balance and various hormonal systems. 

The relationship between the microbiome and metabolic diseases is being studied particularly intensively. 

People with obesity or type 2 diabetes often display changes in microbial composition. At the same time, the concentrations of various microbial metabolic products differ from those found in metabolically healthy individuals.

However, it is often impossible to determine clearly whether these changes are a cause or a consequence of disease. 

The relationship is probably bidirectional. 

A low-fibre diet changes the microbiome. At the same time, a disrupted microbiome alters the production of important metabolites, which may in turn influence metabolism.

The connection between the gut and the brain

The gut and the brain communicate continuously with one another. This network is known as the gut–brain axis.

Various systems are involved in this communication:

• the vagus nerve
• the enteric nervous system
• the immune system
• hormones
• microbial metabolic products

Changes in the gut can therefore affect the central nervous system.

Some gut bacteria produce precursors of various neurotransmitters or influence their formation indirectly. Others produce metabolites that can modulate inflammatory processes in the brain or influence the function of the blood–brain barrier.

In recent years, associations have been described between changes in the microbiome and conditions such as depression, Parkinson’s disease and Alzheimer’s disease. 

These findings are scientifically very interesting. Nevertheless, caution is required.

Most studies have so far demonstrated associations. Whether changes in the microbiome actually contribute to the development of these diseases or merely represent a consequence or accompanying feature is currently being studied intensively.

The microbiome and the hallmarks of ageing

The gut microbiome influences several biological processes closely connected with the hallmarks of ageing.

Chronic inflammation

With age, many people develop low-grade chronic inflammation, known as inflammaging.

Changes in the microbiome can intensify this process.

Reduced production of short-chain fatty acids, a disrupted intestinal barrier and increased passage of bacterial components into the bloodstream promote activation of the immune system and increase concentrations of pro-inflammatory cytokines.

This chronic inflammatory activity is in turn considered a risk factor for numerous age-related diseases.

Mitochondrial function

Mitochondria respond sensitively to inflammatory processes and metabolic changes.

Microbial metabolites can influence mitochondrial function both directly and indirectly. Short-chain fatty acids improve energy metabolism in certain tissues and modulate signalling pathways involved in mitochondrial biogenesis.

Research in this area is developing particularly rapidly, although many mechanisms are still under investigation.

Metabolic health

The microbiome influences the release of various gut hormones such as GLP-1 and PYY, which help regulate satiety, blood sugar control and the insulin response.

This creates a close relationship between the microbiome, metabolic flexibility and insulin sensitivity.

Because metabolic disorders are considered major drivers of biological ageing, the microbiome may indirectly contribute to maintaining healthy metabolic function.

Epigenetic regulation

Some bacterial metabolic products influence epigenetic mechanisms.

Butyrate in particular alters the activity of certain histone deacetylases and thereby regulates gene expression in different cell types.

This relationship is one of the most fascinating areas of microbiome research because it shows how nutrition and gut bacteria can influence the long-term activity of human genes without changing the DNA sequence itself.

How does the microbiome change with age?

While the microbiome of healthy adults remains comparatively stable over many years, its composition and function often change significantly in later life.

Typical changes include:

• lower bacterial diversity
• a decline in butyrate-producing bacteria
• an increase in potentially pro-inflammatory microorganisms
• reduced stability of the microbial ecosystem

However, these changes do not occur to the same extent in all older people.

Studies of exceptionally long-lived individuals reveal a more differentiated picture.

Despite their advanced age, many centenarians have remarkably high microbial diversity. They also have increased numbers of bacterial species that produce specialised secondary bile acids. Some of these metabolites may have anti-inflammatory or antimicrobial properties.

Whether these changes actively contribute to longevity or merely accompany it is currently the subject of intensive research.

What do studies of centenarians reveal?

A number of international research projects have investigated the microbiome of exceptionally long-lived people.

The results show that centenarians do not possess a uniform microbiome. Their microbial communities sometimes differ considerably.

Nevertheless, several common features can be identified.

Compared with younger adults, many long-lived people display:

• high functional diversity,
• altered bile acid production,
• increased production of certain bacterial metabolites,
• remarkable stability of the microbial ecosystem

.

These observations provide valuable clues regarding possible relationships between the microbiome and healthy ageing.

However, they do not show whether these microbial characteristics are the cause or the consequence of an overall healthy lifestyle.

Can nutrition influence the microbiome in a targeted way?

Few factors alter the gut microbiome as sustainably as nutrition. The activity of certain bacterial communities can change within just a few days when the composition of the diet changes significantly. Lasting changes, however, generally arise only through long-term dietary habits.

The focus is less on individual foods than on the overall dietary pattern. A varied diet containing many plant-based foods generally promotes greater microbial diversity than a diet consisting mainly of highly processed products.

Fibre is the microbiome’s most important energy source

Fibre is one of the best-studied nutritional factors in microbiome research.

While it passes through the small intestine largely undigested, it is fermented in the large intestine by specialised bacteria. This produces the short-chain fatty acids described above, which have numerous positive effects on the intestinal barrier, metabolism and the immune system.

Foods particularly rich in different types of fibre include:

• vegetables
• legumes
• whole-grain products
• nuts
• seeds
• fruit

Quantity is not the only factor that matters. The diversity of plants consumed is equally important. Different plants contain different fibres and secondary plant compounds, which in turn promote different bacterial species.

Polyphenols as food for selected gut bacteria

Alongside fibre, polyphenols are receiving increasing attention in research.

These are secondary plant compounds found in berries, cocoa, green tea, coffee, pomegranate, olive oil and numerous herbs.

A large proportion of these compounds is converted into biologically active metabolites only by gut bacteria. At the same time, polyphenols promote the growth of certain microorganisms and may inhibit pro-inflammatory bacteria.

This reciprocal relationship illustrates how closely nutrition and the microbiome are intertwined. Many of the health-promoting effects of plant-based foods probably arise only through their processing in the gut.

Fermented foods

Fermented foods are also frequently associated with a healthy microbiome.

Examples include:

• plain yoghurt
• kefir
• sauerkraut
• kimchi
• miso
• tempeh

They contain microorganisms or microbial metabolites that can interact with the gut microbiome.

Several intervention studies suggest that fermented foods may increase microbial diversity and reduce inflammatory markers. However, the products differ substantially in terms of their microorganisms and composition. The results therefore cannot simply be transferred to all fermented foods.

Prebiotics, probiotics and synbiotics

With the growing interest in the microbiome, the range of corresponding food supplements has also increased considerably. However, the scientific evidence is more nuanced than many marketing claims suggest.

Prebiotics

Prebiotics are indigestible food components that selectively support the growth of health-promoting microorganisms.

The best-known prebiotics include:

• inulin
• fructooligosaccharides
• galactooligosaccharides
• resistant starch

They occur naturally in foods including chicory, Jerusalem artichoke, onions, garlic, leeks, oats and green bananas.

Numerous studies show that prebiotics can promote the production of short-chain fatty acids and positively influence microbiome composition.

Probiotics

Probiotics are live microorganisms that may provide a health benefit when consumed in sufficient quantities.

The most commonly used organisms are various species from the genera Lactobacillus and Bifidobacterium, as well as certain yeasts.

However, effectiveness depends heavily on the individual strain, dosage and the condition being studied.

There is good evidence for some applications, such as preventing antibiotic-associated diarrhoea or treating certain forms of irritable bowel syndrome.

For general health improvement or even life extension, however, the available scientific data are insufficient.

Synbiotics

Synbiotics combine prebiotics and probiotics.

The idea is to provide the introduced microorganisms with suitable nutrients at the same time.

Whether this combination is generally superior to individual preparations cannot yet be answered conclusively.

What role do antibiotics play?

Antibiotics are among the strongest influencing factors affecting the gut microbiome.

They combat pathogenic bacteria, but often also affect beneficial microorganisms.

Depending on the active compound, bacterial diversity can decline significantly. Some species recover within a few weeks, while others remain altered for months or even years.

Antibiotics should therefore be used only when they are medically necessary.

After necessary antibiotic treatment, the microbiome can often recover. How quickly this occurs depends on factors including age, diet, the initial condition of the microbiome and the type of antibiotic.

Exercise also influences the microbiome

Physical activity affects not only the heart, muscles and metabolism. The gut microbiome also changes with regular training.

Several studies show that physically active people often have greater microbial diversity than inactive individuals.

Higher concentrations of butyrate-producing bacteria have also been described.

The underlying mechanisms are not yet fully understood. Several factors probably interact, including changes in metabolism, intestinal blood flow, the immune system and nutrition.

Because physical activity also positively influences many hallmarks of ageing, it is not yet possible to determine clearly what proportion of its health effects is mediated directly through the microbiome.

Sleep, stress and the circadian rhythm

The gut flora is influenced not only by nutrition and exercise.

Chronic stress, sleep deprivation and disruptions to the circadian rhythm also alter microbiome composition.

Experimental studies show that even short-term sleep deprivation can alter the metabolic processes of gut bacteria. Chronic psychological stress also influences intestinal motility, intestinal-barrier permeability and various immune reactions.

Communication between the brain and the gut is bidirectional.

Stress changes the microbiome. At the same time, changes in the microbiome can modulate the body’s stress response. This bidirectional interaction is one of the most active fields of modern microbiome research.

At-home microbiome tests: how informative are they?

Numerous commercial microbiome tests have entered the market in recent years.

Most analyse a stool sample to determine the composition of gut bacteria. Consumers then receive individual dietary recommendations or information about supposed imbalances.

From a scientific perspective, however, these services currently have only limited informative value.

There are several reasons for this:

• The microbiome differs considerably from person to person.
• No universally valid ideal profile currently exists.
• Composition fluctuates naturally over time.
• Many bacteria perform similar functions even though they belong to different species.
• The clinical significance of many measured changes remains unclear.

Microbiome analyses are therefore currently primarily an important research tool. For general preventive healthcare, commercial tests so far offer only limited practical benefit.

What are the limits of current microbiome research?

Scientific interest in the microbiome has grown rapidly in recent years. At the same time, the field is one of the most complex areas of modern biomedicine. Many associations that are already presented as established in the media are still being clarified scientifically.

One major reason is the enormous diversity of the microbiome. No two people have exactly the same microbial composition. Age, nutrition, genetics, medication, environment, sleep, physical activity and numerous other factors influence microbial communities simultaneously.

This often makes it difficult to separate cause from effect.

If, for example, people with type 2 diabetes have an altered microbiome, the question is whether these changes contributed to the disease or arose only as a result of the disease, diet or medication.

Correlation does not mean causation

A large proportion of the available studies are based on observational data.

These investigations provide valuable clues regarding associations between certain bacteria and diseases. However, they generally cannot prove that a microorganism is actually the cause of a health-related change.

Only controlled intervention studies allow more robust conclusions. Such studies are considerably more difficult in microbiome research because the intestinal ecosystem changes under the influence of numerous factors at the same time.

In addition, the composition of microorganisms is not the only decisive factor. Their function is equally important.

Two people may differ considerably in terms of bacterial species and still have comparable metabolic functions. Research is therefore increasingly moving away from merely identifying individual bacterial species and instead examining their metabolic activity and the metabolites they produce.

Not every bacterium is inherently good or bad

Popular accounts often describe individual bacteria as clearly beneficial or harmful.

The scientific reality is much more complex.

Many microorganisms perform different functions depending on diet, metabolic conditions or the composition of the remaining gut flora. Some species may have health-promoting effects under certain conditions but provide no demonstrable benefit or even become problematic under others.

Modern microbiome research therefore increasingly focuses on functional networks rather than individual microorganisms.

What significance does the microbiome have for preventive medicine?

Although many questions remain unanswered, a clear trend is already emerging.

The microbiome is not an isolated organ and is not an independent switch for health or disease. It responds to almost all lifestyle factors while simultaneously influencing numerous physiological processes.

This is precisely why it is particularly important for preventive medicine.

Measures that have long been associated with a lower risk of chronic disease often also promote a diverse and functionally stable microbiome.

These include in particular:

• a fibre-rich, plant-focused diet,
• regular physical activity,
• sufficient sleep,
• as stable a day–night rhythm as possible,
• restrained use of antibiotics when they are not medically required,
• the treatment of chronic diseases and promotion of metabolic health.

It is noteworthy that these recommendations are already supported by a large number of high-quality studies independently of the microbiome. The gut microbiome provides an additional biological explanation for why these lifestyle factors have such far-reaching effects on health.

Conclusion

The gut microbiome is one of the most fascinating fields of research in modern medicine. The trillions of microorganisms in the gut perform far more functions than supporting digestion. They influence the function of the intestinal barrier, regulate the immune system, produce bioactive metabolic products and communicate closely with metabolism, the brain and numerous other organs. 

The microbiome is receiving increasing scientific attention particularly in relation to healthy ageing. Its metabolic products influence processes closely connected with the hallmarks of ageing. These include chronic inflammation, mitochondrial function, metabolic regulation and epigenetic mechanisms. At the same time, studies of long-lived people show that a functionally diverse microbiome is often associated with better health in advanced age. 

Nevertheless, the current evidence should be interpreted realistically. The microbiome is neither the sole cause of longevity nor can health be reduced to individual bacterial species. Rather, the composition of the gut flora reflects the interaction of nutrition, exercise, sleep, medication, environment and genetic factors.

From today’s perspective, the most convincing scientific data suggest that the microbiome can be influenced positively above all through an overall healthy lifestyle. A varied, plant-focused diet rich in fibre, regular physical activity, sufficient sleep and responsible use of antibiotics not only promote microbial diversity but also improve numerous other health parameters. 

It is precisely this close interconnection that makes the microbiome so interesting for longevity research. It links nutrition, metabolism, immunology and ageing biology into a shared biological network and opens up new perspectives for preventing age-related diseases. Many mechanisms are still under investigation. However, it is already clear that a healthy microbiome is not an isolated therapeutic target but an expression of a lifestyle that supports the health of the entire organism.

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