Abstract
INTRODUCTION: The gut microbiome undergoes dynamic changes with aging across diverse healthy populations. However, data from Saudi Arabia remain limited. This pilot study investigated age-related variations in the gut microbiome among healthy Saudi adults to characterize region-specific microbial signatures and identify taxa potentially associated with aging in a healthy population. METHODS: We established the Saudi Aging and Microbiome Study (SAMS) to investigate age-related changes in fecal microbiome of Saudi adults. In this pilot phase, 145 healthy participants aged 19-69 years were enrolled. Shotgun metagenomic sequencing was performed to profile fecal microbiome at the species level. Microbial diversity and taxonomic composition were compared across five age groups. Spearman and confounder-adjusted partial Spearman correlation were applied to identify taxa significantly associated with chronological age. RESULTS: We analyzed fecal microbiome of 145 healthy adults distributed among five age groups: G1 (19-29 years, n = 33; 22.7%), G2 (30-39 years, n = 30; 20.7%), G3 (40-49 years, n = 27; 18.6%), G4 (50-59 years, n = 31; 21.4%), and G5 (60-69 years, n = 24; 16.6%). Of these, 75 (51.7%) were male, and 70 (48.3%) were female. Alpha diversity increased from young to older adulthood for observed richness and Shannon indexes (all q < 0.05). Beta diversity also varied significantly with age (PERMANOVA R (2) = 0.13, q = 0.023), indicating distinct microbial community structures in healthy older adults. At the phylum level, Firmicutes significantly increased with age (FC = 1.35; q = 0.026), whereas Bacteroidota decreased (FC = 0.59; q = 0.01). Consistent with these trends, Blautia obeum showed positive correlations, while Bacteroides thetaiotaomicron and Phocaeicola vulgatus showed negative correlations with chronological age. CONCLUSION: In healthy Saudi adults, increasing age was associated with higher microbial diversity and compositional shifts at phylum and species levels. These age-associated microbial taxa might represent biomarkers of healthy aging and suggest an enhanced community capacity for short-chain fatty acids (SCFAs) production, a hypothesis warranting validation through future functional analyses.