Abstract
This Review discusses the current state of knowledge on the contribution of the gut microbiome as a potential key actor in defining how we age. The gut microbiome is a complex ecosystem that establishes lifelong dynamic interactions with the host at multiple levels (several gut–organ axes), differently influencing ageing patterns and age-related disease onset and progression across populations. Accordingly, the definition of a ‘normative’ gut microbiome remains elusive, depending largely on the interaction with the external environment. In this complex scenario, the causal role of the gut microbiome in defining the ageing trajectory and its precise contribution to various organ-specific age-related diseases is still uncertain in clinical terms and could be context specific. Multiparametric and uniqueness indexes within a given population have shown a certain capacity for predicting disability and mortality. However, the gut microbiome is shaped over time by exposure to different intrinsic and environmental factors, resulting in a high degree of inter-individual variability, a key phenomenon that should be considered to develop novel personalized strategies to counteract age-related disease and frailty.
Key points
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Ageing is associated with a reconfiguration of the gut microbial communities towards dysbiosis. This process is influenced by life-long environmental exposures and is highly individualized, resulting in elevated inter-individual microbiome variability.
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Gut microbiome reconfiguration during ageing is influenced by gastrointestinal cell senescence and provides a great amount of antigenic stimulation to the senescent immune system, fuelling inflammageing and favouring trajectories towards the frailty syndrome.
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The gut microbiome of centenarians shows an exceptional capacity of adaptation to the pathophysiological processes leading to inflammageing, with persistence of a set of bacterial taxa with anti-inflammatory properties.
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The dynamic interaction among lifestyle, gut microbiome and cell and organ senescence could influence the adaptation of each individual to the biological mechanisms of ageing, resulting in different clinical trajectories towards health or disease.
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Modulation of the gut microbiome with diet, exercise and nutritional supplements containing probiotics, prebiotics or food bioactives could represent an effective strategy to improve the ageing trajectory in older individuals.
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Microbiome-centred interventions should be personalized and take into account the inter-individual variability of microbial responses. Microbiome profiling and metabotyping should be increased to enable more efficient translation of microbiome science into clinical practice.
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A.T. and C.F. researched data for the article. S.M., G.Z., A.N. and C.F. contributed substantially to discussion of the content. A.T. wrote the article. S.M., G.Z., A.N. and C.F. reviewed and/or edited the manuscript before submission.
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Ticinesi, A., Maggi, S., Nouvenne, A. et al. The gut microbiome and ageing trajectories: mechanisms and clinical implications. Nat Rev Endocrinol (2026). https://doi.org/10.1038/s41574-026-01236-x
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DOI: https://doi.org/10.1038/s41574-026-01236-x
