Postbiotic Bifidobacterium. breve 207–1 ameliorates high glucose-induced glycolipid metabolic disorders in C. elegans via the daf-2/daf-16 signaling pathway

The present study demonstrates that postbiotic Bifidobacterium. breve 207–1 (250, 500, 1000 μg/mL) ameliorates high glucose diet-induced glycolipid metabolic disorders in Caenorhabditis elegans by converging glucose metabolism, lipid homeostasis, and oxidative stress resolution onto the conserved daf-2/daf-16 signaling axis. The postbiotic demonstrated a substantial reduction in glucose, glycogen, and triglycerides, while concurrently suppressing ROS/lipofuscin accumulation and extending lifespan. Mechanistically, by inhibiting the insulin receptor daf-2 and subsequent activation of the transcription factor daf-16 , the postbiotic enhanced glycolytic flux ( hxk-2, gpd-2, pyk-2 ) while concurrently suppressing glycogenesis ( gsy-1, pygl-1 ), promoted β-oxidation ( acs-2, cpt-4 ) yet inhibited lipogenesis ( mdt-15/sbp-1, fat-7 ), and induced antioxidant defense ( sod-3 ), ultimately disrupting the vicious cycle between metabolic dysfunction and oxidative damage. These findings position B. breve 207–1 as a promising postbiotic intervention for metabolic syndrome, providing molecular insights for targeting the insulin/FOXO pathways. Molecular mechanisms by postbiotic B. breve 207–1 improves glycolipid metabolism in C. elegans . “↑” in boxes represent upregulation, and “↓” in boxes represent downregulation. Other are connecting lines. • Ameliorates high-glucose-induced glycolipid metabolic disorders in C. elegans . • Reduced the accumulation of glucose, glycogen, triglyceride and ROS. • Extends lifespan and attenuates aging-related lipofuscin deposition. • Coordinates the regulation of glucolipid metabolism and antioxidant defense via the daf-2/daf-16 pathway.