Dietary ellagic acid improves glucose and lipid homeostasis with concurrent gut microbiota and serum metabolome remodeling in db/db mice

This study evaluated dietary ellagic acid (EA) as a food-derived polyphenol for improving glucose and lipid metabolic abnormalities using complementary in vitro , C. elegans , starch-loading, and db/db mouse models. EA inhibited alpha-glucosidase activity and attenuated starch-induced postprandial hyperglycemia. In C. elegans , EA reduced lipid accumulation and glucose storage while preserving feeding-related physiological indicators. In db/db mice, 8-week EA administration improved fasting blood glucose, dyslipidemia, insulin-related indices, and serum GLP-1 compared with diabetic controls. Cecal 16S rRNA gene sequencing and untargeted serum metabolomics further showed that EA intervention was accompanied by shifts in microbial composition and broad remodeling of amino acid, lipid, and glycerophospholipid-related metabolic features. Correlation analysis linked selected bacterial genera and lipid-related metabolites, including several lysophosphatidylcholine species, with GLP-1, fasting blood glucose, and insulin resistance-related markers. These findings support EA as a functional-food candidate associated with coordinated host-microbial metabolic remodeling in diabetic mice. Because the study did not include receptor blockade, microbial-dependence experiments, targeted lysophosphatidylcholine quantification, or urolithin profiling, the microbiota-metabolite-GLP-1 relationship should be interpreted as a candidate mechanism requiring further validation.