Multi-modality profiling identifies Neisseria flavescens as a central geroprotective oral commensal in humans.

Abstract

Aging is accompanied by progressive physiological decline, yet the microbiome determinants that modulate aging remain unclear. Here, we identify Neisseria flavescens (Nf) as an oral commensal associated with decelerated aging in humans. Using AURORA, a generative multi-modality framework, we developed multi-modality aging clocks, performed in silico screening for age-gap-reducing interventions and predicted Nf as a top hit. In silico perturbations linked increased Nf abundance to favorable physiological signatures, beneficial gut taxa and biosynthesis of beneficial metabolites. We isolated two Nf strains and validated their production of beneficial metabolites. Functional assays demonstrated that live Nf extended lifespan and healthspan in Caenorhabditis elegans. In aged mice, heat-killed Nf supplementation restored the serum metabolome, liver transcriptome and gut microbiome toward younger states. By establishing an AI-driven intervention discovery engine and identifying Nf as a geroprotective microorganism, these findings highlight the oral microbiome as an underestimated axis of systemic aging and a candidate for geroprotective interventions.