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Article Abstract

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 , 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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12270803PMC
http://dx.doi.org/10.1016/j.isci.2025.112985DOI Listing

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