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Activated vitamin D3 improves the microbiota and intestinal barrier in type 2 diabetic mice via modulating AMPK activation

Year: 2025

Type: article

Abstract: The association between vitamin D and type 2 diabetes mellitus (T2DM) pathogenesis, particularly through gut microbial interactions, requires further elucidation. This study investigates vitamin D-microbial interactions in T2DM pathogenesis, targeting their modulation of inflammatory cascades and redox imbalance. After successfully establishing a T2DM mouse model using a high-fat diet (HFD)/streptozotocin (STZ), the mice were treated with activated Vitamin D 3 (1,25(OH) 2 D 3 ) for 4 weeks. Systemic parameters including glycemic control (FBG, GHbA1c, insulin), oxidative stress biomarkers (ROS, MDA, T-AOC, CAT), proinflammatory cytokines (TNF-α, TNF-β), and lipopolysaccharide (LPS) levels were measured. Microbial community profiling via 16 S rRNA sequencing, while colonic redox status (MDA/SOD), barrier integrity (ZO-1/Occludin), and metabolic signaling (SIRT1, p-AMPK) were analyzed. T2DM mice exhibited gut microbial dysbiosis, marked by significant enrichment of Enterococcus and Enterobacter , whose abundances correlated positively with hyperglycemia, inflammation, and oxidative stress. Histopathological analyses concurrently demonstrated compromised intestinal barrier integrity, characterized by reduced ZO-1/Occludin protein expression and SOD activity. Notably, treatment with 1,25(OH) 2 D 3 effectively mitigated these pathological changes and concurrently enhanced AMPK phosphorylation in the colon. These findings position vitamin D-AMPK axis modulation as a promising therapeutic strategy for microbiota-metabolism crosstalk in T2DM, highlighting its translational potential for clinical validation.

Source: Scientific Reports

DOI: 10.1038/s41598-025-27937-3