Healthy ageing and longevity depends on complex interactions between host genetics, the gut microbiome, and environmental factors (1,2). While specific microbial functions such as short-chain fatty acid production and bile acid metabolism are linked to resilience, the causal mechanisms that connect host genetic variation, microbial activity, and ageing phenotypes remain unclear. This project will integrate gut metagenomic, host genetic, and phenotypic data to uncover the biological pathways that drive healthy ageing.
Using AI and systems modelling (3), we will map how genetic variation influences microbial metabolism and identify microbial functions that protect against age-related decline in cognition, metabolism, and immune function (4,5). We will develop computational models that simulate host–microbe metabolic interactions and predict the impact of interventions, such as diet, probiotics, or microbiome-targeted therapeutics, on protective microbial functions.
The culmination of this work will be a digital twin of the ageing, capable of forecasting individual responses to interventions and providing clinicians with interpretable, data-driven insights into modifiable biological pathways and longevity.
This integrative, AI-enabled approach represents a major advance over descriptive microbiome studies, offering a mechanistic and predictive framework for precision healthy ageing. The project will ultimately contribute to personalised strategies that maintain resilience and delay the onset of age-related multimorbidity (6).