Abstract / Summary
The gut microbiome undergoes compositional and functional changes with ageing. However, microbial signatures specifically associated with healthy ageing, independent of age-related diseases, remain poorly defined. This systematic review aimed to identify compositional and functional features of the gut microbiome associated with healthy ageing. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic search was conducted using PubMed, Web of Science and ScienceDirect for studies published up to January 2026. The search strategy focused on gut microbiome, ageing and healthy terms. Risk of bias was assessed using the Newcastle-Ottawa Scale. Gut microbiome composition was reviewed across five predefined age groups, while the functional pathways were reviewed for older adults and centenarians. The included studies represented several regions, including recognized longevity hotspots, although geographic representation remained limited. Most studies used 16S rRNA gene sequencing (n=24; 58.5%), followed by shotgun metagenomics (n=13; 31.7%), both (n=3; 7.4%) or metaproteomics (n=1; 2.4%). Enrichment of specific taxa such as Akkermansia, Alistipes and Parabacteroides was consistently reported in centenarians, alongside distinct patterns in older adults and long-lived individuals. Functional profiling suggested differences in pathways related to amino acid catabolism, vitamin biosynthesis and pathways potentially linked to immune modulation, inflammatory processes and gut barrier support. This review provides the first structured synthesis of gut microbiome signatures associated with healthy ageing across the lifespan, highlighting consistent functional traits and the need for a wider geographic representation in future research. It supports standardized, multi-omics framework to identify robust biomarkers and potential microbiome-based interventions for promoting healthy ageing.