Dietary Purple Sweet Potato Anthocyanin Extracts Attenuate Intestinal Barrier Decline in Naturally Aged Mice Via the Microbiota-Autophagy-Stem Cell Axis

Abstract

Age-related deterioration of the intestinal epithelial barrier exacerbates systemic metabolic and functional decline, highlighting the gut as a key target for dietary interventions in healthy aging. Here, using naturally aged mice and intestinal organoids, we demonstrate that supplementation with purple sweet potato anthocyanins (PSPAs) alleviates systemic aging phenotypes, including impaired motor coordination, hepatic lipid dysregulation, insulin resistance, and cellular senescence, while concurrently restoring intestinal barrier integrity. PSPAs enhanced tight junction protein expression and epithelial architecture, independently of inflammation resolution, and promoted the proliferative and differentiation capacity of intestinal stem cells (ISCs). Metagenomic profiling revealed that PSPAs remodeled aging-associated gut microbiota composition and functions. Fecal microbiota transplantation established the causal contribution of microbiota remodeling to ISC rejuvenation, while luminal content-organoid assays confirmed the role of microbial metabolites. Integrative metabolomics identified autophagy-linked metabolic signals, including short-chain fatty acids, with the PI3K-AKT pathway emerging as a central regulatory hub. Collectively, this multi-omics study establishes a mechanistic framework in which PSPAs alleviate aging-associated barrier decline through a "microbiota-autophagy-stem cell" axis, providing important insights into polyphenol-based strategies for gut-centered healthy aging.