Low-carbohydrate-high-protein diet accelerates diabetic vascular calcification via gut microbiota-dependent TUDCA depletion

Depletion of F. rodentium attenuated, whereas colonisation aggravated, aortic calcification and VSMC phenotypic switching. Metabolomics demonstrated that F. rodentium possesses bile salt hydrolase activity, hydrolysing tauroursodeoxycholic acid (TUDCA) to ursodeoxycholic acid, thereby reducing circulating TUDCA. TUDCA supplementation suppressed excessive endoplasmic reticulum (ER) stress, blocked VSMC osteogenic differentiation, and alleviated VC.

In vitro experiments confirmed that TUDCA dose-dependently suppressed VSMC calcification by inhibiting ER stress. LC‑HPD accelerates diabetic VC by enriching F. rodentium, which depletes TUDCA and thereby unleashes ER stress‑driven VSMC osteogenesis. These findings identify the TUDCA/ER stress axis as a potential therapeutic target for diabetic vascular complications, suggesting that related microbiota–bile acid mechanisms in humans warrant further investigation.