Mouth Bacteria Neisseria flavescens Found to Slow Aging in Animals and Humans

Aging rates differ widely between people of the same chronological age, which suggests biological aging can be modified. The gut microbiome is a known regulator of healthspan, but the oral cavity, the body's second largest microbial habitat, has received little attention as a driver of systemic aging. This study asks whether specific oral bacteria slow aging, and whether an AI-driven discovery pipeline can find them and then be tested in living organisms.

The team sequenced tongue-coating metagenomes from a Jidong, China cohort: 194 usable samples from 2018 and 478 from 2019. The 2019 group was enriched for fast and slow agers as judged by 3D facial aging clocks. Plasma was profiled by NMR, yielding 346 metabolites. Using their generative multimodal model AURORA, the authors built aging clocks for each data type and quantified aging rate as cAgeDiff, where negative values mean slower aging. Oral microbiome and metabolome features correlated more strongly with biological age than with chronological age.

Neisseria flavescens (Nf) showed negative associations with cAgeDiff across nearly all clock modalities. Slow agers had lower species richness with stable Nf dominance, while fast agers had higher Shannon entropy (P = 3.63 × 10^-18; 133 per group) and a more disordered co-occurrence network. Nf abundance was strongly lower in smokers and weakly lower with longer teeth-brushing time, but was not clearly tied to income or diet. In silico perturbation then ranked 90 features that shifted cAgeDiff. Nf and Megasphaera micronuciformis were the top species reducing it, with no sex difference (P = 0.19). Simulated Nf increases predicted lower gamma-glutamyl transferase, alkaline phosphatase, triglycerides and BMI, higher HDL and ApoA, and reduced fatty liver and hyperlipidemia risk. In independent Human Microbiome Project data (87 paired gut-oral samples), Nf had the largest effect on lowering gut microbiome age. It also enriched Akkermansia muciniphila and depleted an 'unhealthy gut' signature (NES = -1.62, P = 0.017).

The authors isolated two complete-genome Nf strains, a11 and e5, from healthy volunteers' tongues. RNA-seq and mass spectrometry confirmed upregulated tryptophan, biotin and vitamin B6 pathways. Culture supernatants had higher tryptophan, indole-3-acetic acid (IAA) and vitamin B6 than E. coli OP50 controls (IAA P = 3.2 × 10^-6 and 1.0 × 10^-7; n = 3 cultures).

In C. elegans, live Nf extended average lifespan by 39.35% (a11) and 26.2% (e5). Day-15 gut leakage fell from 41.6% on OP50 to 15.8% with a11 (P < 0.05), while e5 (25%) was not significant (P = 0.15). Mobility improved at days 10 and 12. Treated worms were larger, which argues against dietary restriction as the cause. Both strains reversed age-related gene expression (PCC -0.637 and -0.502). Worms lacking the IAA receptor AHR-1 lost only part of the barrier benefit, implying other metabolites contribute. Heat-killed Nf kept roughly half the lifespan effect. In 20-month-old male mice (n = 6 per group), 10 weeks of heat-killed Nf in drinking water lowered serum triglycerides with a11. It partially restored A. muciniphila and Bifidobacterium pseudolongum and partly reversed age-related liver gene changes. Body weight did not change.

Important caveats apply. Human findings are observational and the causal claims rest on AI simulation. Animal work used small groups, only male mice and heat-killed bacteria, and the mouse reversal was partial. No human intervention trial exists.