Progressive gut microbiota shifts and functional alterations across aging stages and frailty in mice

Summary: The gut microbiota modulates aging through metabolic and immune interactions. To characterize microbial changes during aging, we profiled gut microbiota across four stages in male C57BL/6J mice: young-adult, middle-aged, senescent, and frailty. Using 16S rRNA sequencing and targeted metabol...

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Main Authors: Xinwei Jiao, Hongyu Li, Ting Wang, Hongchen Fu, Shiwu Wang, Hong Liu, Lei Wang, Xiuyun Li, Aijun Deng, Zhijie Li
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004225012465
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Summary:Summary: The gut microbiota modulates aging through metabolic and immune interactions. To characterize microbial changes during aging, we profiled gut microbiota across four stages in male C57BL/6J mice: young-adult, middle-aged, senescent, and frailty. Using 16S rRNA sequencing and targeted metabolomics, we observed a biphasic diversity pattern, with reduced richness in senescence followed by a rebound in frailty. Frailty-stage microbiota showed increased connectivity and enrichment of Lachnospiraceae, alongside short-chain fatty acid (SCFA) depletion, particularly butanoic acid. Functional predictions revealed elevated immune activity and reduced carbohydrate metabolism, linked to specific microbial taxa. These findings highlight a structured remodeling of the gut microbiota during aging, with frailty representing a distinct dysbiotic state associated with metabolic dysfunction. Modulating gut microbial composition may represent a potential strategy to attenuate frailty and promote healthy aging.
ISSN:2589-0042