The B. pseudocatenulatum–5-AVAB axis was identified as a promising target for microbiome-based interventions to promote healthy aging, with both the probiotic and its metabolite counteracting inflammaging to extend healthspan in aged mice.
A microbiome-based aging clock (MicroAge) was developed to track biological aging trajectories using enterotype-specific gut microbial remodeling data.
Bifidobacterium pseudocatenulatum was identified as a candidate geroprotective species that is consistently depleted during aging.
Oral B. pseudocatenulatum monotherapy in naturally aged mice rescued intestinal homeostasis and mitigated multiorgan inflammaging.
B. pseudocatenulatum treatment enhanced cognitive-motor performance and extended healthspan in naturally aged mice.
5-Aminovaleric acid betaine (5-AVAB) was characterized as a key B. pseudocatenulatum-derived metabolite whose levels decline physiologically during aging in humans.
5-AVAB supplementation partially recapitulated the systemic benefits of B. pseudocatenulatum treatment, including improved cognitive and motor function and suppressed multiorgan inflammaging.
The B. pseudocatenulatum–5-AVAB axis was identified as the mechanistic basis for the probiotic's geroprotective effects and as a promising intervention target.
This research suggests that a specific gut bacterium called Bifidobacterium pseudocatenulatum naturally decreases in abundance as people age, and that this loss may contribute to the chronic low-grade inflammation associated with aging (called 'inflammaging') that drives many age-related diseases. The researchers tracked gut microbiome changes in multiple groups of Chinese adults, built a biological aging clock based on gut bacteria, and identified B. pseudocatenulatum as consistently depleted in older individuals regardless of sex. When they gave this bacterium as an oral probiotic to naturally aged mice, it improved gut health, reduced inflammation across multiple organs, boosted both memory and physical movement, and extended the animals' healthy lifespan. The study also identified the specific molecule through which this bacterium exerts its effects: a compound called 5-aminovaleric acid betaine (5-AVAB), which B. pseudocatenulatum produces and which also declines in aging humans. When 5-AVAB was given directly as a supplement to aged mice, it reproduced many of the same benefits as the probiotic itself — reducing multiorgan inflammation and improving cognitive and motor performance — though not all of them, suggesting 5-AVAB is an important but not the only mechanism. This research suggests that restoring B. pseudocatenulatum or supplementing with its metabolite 5-AVAB could be a strategy for promoting healthier aging by targeting gut-driven inflammation. The identification of a specific microbe-metabolite axis provides a concrete biological pathway that could potentially be targeted with probiotics or metabolite-based therapies, though the current evidence comes primarily from mouse experiments and human observational data, and clinical trials in humans would be needed to confirm these effects.
Lu X, Ping J, Han Z, Zhang S, Liu L, Xiong M, et al.. (2026). A geroprotective probiotic and its functional metabolite counteract inflammaging to extend healthspan.. Nature aging. https://doi.org/10.1038/s43587-026-01181-4