How Does the Gut Microbiome Influence Immune and Metabolic Health During Ageing?

The gut microbiome changes throughout life

The gut microbiome develops rapidly early in life and becomes relatively stable during adulthood.

With ageing, it tends to become less resilient and more heterogeneous between individuals. Changes may include lower microbial diversity, loss of beneficial microorganisms and expansion of opportunistic pathogens.

These patterns vary considerably between people. Genetics, immune status, diet, environment and metabolic health can all influence how the microbiome changes with age.

Ageing and microbiome changes can reinforce each other

The relationship between ageing and microbiome imbalance appears to be bidirectional.

Microbiome disruption may promote inflammation and impair intestinal health. At the same time, age-related deterioration in immune function and intestinal barrier integrity can change the gut environment and further disrupt the microbiome.

This may create a self-reinforcing ageing–dysbiosis cycle.

The microbiome interacts with immune ageing

Immunosenescence involves progressive changes in both innate and adaptive immune function.

The gut microbiome interacts with immune cells, inflammatory pathways and the intestinal barrier. Changes in these interactions may contribute to immune dysfunction and persistent low-grade inflammation during ageing.

Immune ageing can also reshape the intestinal environment and microbiome.

Microbial metabolites connect the microbiome with metabolic health

Metabolic homeostasis also changes with age.

Microbiome imbalance may reduce beneficial metabolites, including short-chain fatty acids and tryptophan-derived metabolites, while increasing potentially harmful products such as lipopolysaccharide and some secondary bile acids.

These microbial metabolites act as important signalling mediators. They can influence host metabolic pathways and mitochondrial function.

The biological effects of the microbiome therefore depend not only on which microorganisms are present, but also on what they produce.

Immune and metabolic ageing are interconnected

Immune regulation and metabolic homeostasis do not operate independently.

Microbial metabolites can influence both systems. Metabolic dysfunction can promote inflammatory activity, while persistent inflammation can interfere with metabolic regulation.

The microbiome may therefore participate in the connection between immune dysfunction, metabolic imbalance, chronic low-grade inflammation and mitochondrial dysfunction during ageing.

Microbiome changes may affect health beyond the intestine

Age-related microbiome changes have been linked with cardiovascular disease, chronic inflammatory disorders, cognitive impairment, neurodegenerative disease and cancer.

These associations support a broader view of the microbiome as part of communication networks connecting the gut with other organs.

Some microbiome features may also have future value as biomarkers. However, an association with disease does not establish causality.

Can the ageing microbiome be modified?

The microbiome remains biologically responsive to external influences.

The review discusses diet, physical activity, probiotics, prebiotics, fecal microbiota transplantation and other interventions as potential approaches to maintaining or restoring microbial homeostasis.

The authors identify microbiome-targeted interventions as promising strategies for the prevention and treatment of age-related disease.

Responses differ between individuals, and the strength of clinical evidence varies between interventions. This supports the need for more personalized approaches and further clinical validation.

Multi-omics may provide a more precise picture

Conventional microbiome analysis provides valuable information about microbial composition and function. However, it has limited ability to determine where and when specific microbiome–host interactions occur.

The authors highlight the integration of metagenomics with other molecular data.

In particular, spatial and spatiotemporal multi-omics may allow microbiome–host interactions to be studied with greater spatial and temporal resolution.

These technologies may help identify how microbiome activity changes during ageing and how these changes differ between individuals.

Healthy ageing depends on maintaining function across interconnected biological systems.

This review places the gut microbiome at the intersection of immune regulation, metabolic homeostasis, inflammation and mitochondrial function.

It also shifts attention from microbial composition alone toward microbial function. What microorganisms produce, how these products interact with host cells and how these interactions change over time may be particularly important.

The relationship works in both directions. Ageing can reshape the microbiome, while microbiome changes may influence biological processes associated with ageing.

Future microbiome assessment may increasingly combine microbial composition, microbial function, metabolites and host biological data.

The authors also highlight the potential of personalized microbiome-targeted strategies for the prevention and treatment of age-related disease.

Spatial and spatiotemporal multi-omics may help reveal where and when microbiome–host interactions occur. This could provide a more precise framework for understanding individual ageing trajectories.

However, microbiome associations do not establish causality. Specific interventions still require stronger clinical evidence before they can be considered established strategies for promoting healthy human ageing.