A geroprotective probiotic and its functional metabolite counteract inflammaging to extend healthspan.

Xiaoyong Lu, Jun Ping, Zichu Han, Shuo Zhang, Lixiao Liu, Muzhao Xiong, Yanling Fan, Jiaming Li, Xiaoyan Sun, Peng Yang, Kejie Zheng, Zheng-Kai Wang, Jiale Ping, Yu Xiong, Yuesheng Zuo, Min Zhang, Jingyi Li, Qi Wu, Qiaoran Wang, Dan-Dan Gao, Beier Jiang, Shuhui Sun, Shuai Ma, Si Wang, Jing Qu, Yun-Gui Yang, Feng Zhang, Guang-Hui Liu, Weiqi Zhang

Beijing Key Laboratory of Intelligent Governance and Application of Biological Big Data, China National Center for Bioinformation and Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China. · pubmed

Paper

Abstract

The gut microbiome profoundly influences host aging, yet the specific microbes and mechanisms governing divergent aging trajectories remain elusive. In this study, we delineated enterotype-specific gut microbial remodeling during aging and developed a microbiome-based aging clock (MicroAge) to track biological aging trajectories. We identified Bifidobacterium pseudocatenulatum (B. pseudocatenulatum) as a candidate geroprotective species consistently depleted during aging across both sexes and multiple Chinese cohorts. In naturally aged mice, oral B. pseudocatenulatum monotherapy rescued intestinal homeostasis, mitigated multiorgan inflammaging, enhanced cognitive-motor performance and extended healthspan. Mechanistically, we characterized 5-aminovaleric acid betaine (5-AVAB) as a key B. pseudocatenulatum-derived metabolite whose levels decline physiologically in aging humans. 5-AVAB supplementation partially recapitulated a broad spectrum of the systemic benefits observed with B. pseudocatenulatum treatment, including improved cognitive and motor function and suppressed multiorgan inflammaging. Our findings identify the B. pseudocatenulatum-5-AVAB axis as a promising target for microbiome-based interventions to promote healthy aging.

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Research summary

The administration of the probiotic Bifidobacterium pseudocatenulatum or its metabolite 5-aminovaleric acid betine extends healthspan and mitigates inflammaging in mice by restoring intestinal homeostasis. This work represents an incremental advance in the field of microbiome-based geroprotection, identifying a specific bacterial strain and metabolite associated with healthy aging, but it lacks the transformative novelty or robust human translational data required for higher impact scores.

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