Age-related diversity of the oral and gut microbiome and its correlation with systemic fatty acids and cytokine profiles in healthy subjects

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Advances in human microbiome research have highlighted its influence on host health. This study aimed to characterize the oral microbiome (OM) and gut microbiome (GM) and to examine their relationships with systemic fatty acid and cytokine profiles across different age groups in healthy adults. Participants aged 18–76 years without diagnosed diseases were grouped into young (18–29 years), middle-aged (30–49 years), and older adults (≥50 years). Blood, dental plaque, and fecal samples were collected. OM and GM composition were evaluated using 16 rRNA sequencing. Circulating free fatty acids (FFAs) were quantified by gas chromatography–mass spectrometry, and serum cytokines were assessed using flow cytometry. In the OM, Fusobacterium and Haemophilus were notably abundant in young adults, while Haemophilus and Neisseria predominated in middle-aged adults. In older adults, Neisseria and Capnocytophaga were the most prevalent oral genera. In the GM, Bacteroides was the most prevalent genus across all age groups, followed by Faecalibacterium , Blautia , and Prevotella_9 . Additionally, circulating levels of decanoic, hexadecanoic, and octadecanoic acids, as well as the cytokine IP-10, were higher in young adults compared with the other age groups. To our knowledge, this study is the first to characterize and correlate the diversity of both the OM and GM with systemic FFA and cytokine profiles in a cohort of healthy adults, highlighting the critical role of age in shaping microbiome composition and associated metabolites. Integrating microbiota profiling with serum FFA and cytokine measurements enhances our understanding of how the microbiome may influence health and disease risk across the adult lifespan. • Distinct age-related differences were observed in dominant oral bacterial taxa, whereas the gut microbiota remained relatively stable across age groups. • Younger adults exhibited higher levels of decanoic acid and IP-10, along with lower abundances of hexadecanoic and octadecanoic acids. • Age significantly influences microbiome composition as well as systemic biomarkers, including free fatty acids and cytokines. • Integrating microbiome, fatty acid, and cytokine data provides deeper insight into age-related physiological changes and potential disease risk.