{
  "abstract": "Background Type 2 diabetes mellitus (T2DM) markedly accelerates atherosclerotic progression and increases plaque instability, which underlies most acute cardiovascular events. Beyond metabolic abnormalities, vascular smooth muscle cell (VSMC) phenotypic switching and chronic inflammation are key determinants of plaque vulnerability. Emerging evidence suggests that gut microbiota dysbiosis contributes to cardiometabolic diseases; however, the mechanistic pathways by which specific microbial metabolites directly influence vascular remodeling under diabetic conditions remain poorly defined.Methods Male ApoE −/− mice were used to establish a diabetic atherosclerosis model through high-fat diet feeding combined with low-dose streptozotocin injection. Gut microbiota composition was manipulated by antibiotic treatment followed by selective Bacteroides vulgatus depletion or supplementation. Circulating levels of the microbial metabolite 4-methylcatechol (4MC) were quantified by targeted metabolomics. Plaque stability was evaluated by histological analysis of fibrous cap thickness, necrotic core area, and macrophage infiltration. Primary VSMCs were treated with 4MC to assess phenotypic switching, and Notch signaling activity was examined using molecular and pharmacological approaches.Results Diabetic ApoE −/− mice exhibited a significant reduction in B. vulgatus abundance, accompanied by decreased circulating 4MC levels. Selective depletion of B. vulgatus further aggravated plaque instability, as evidenced by a 35-40% reduction in fibrous cap thickness, an expansion of necrotic core area, and an approximately 1.8-fold increase in macrophage infiltration compared with non-diabetic controls (P<0.05). In contrast, restoration of B. vulgatus or 4MC supplementation partially reversed these pathological changes. In VSMCs, 4MC treatment promoted a contractile phenotype, with ~1.6-fold upregulation of α-SMA and SM22α and ~40% suppression of synthetic markers, including osteopontin and vimentin. Mechanistically, diabetic conditions induced aberrant activation of Notch signaling, which was attenuated by 4MC. Pharmacological inhibition of Notch signaling mimicked the protective effects of 4MC, whereas pathway activation abolished 4MC-mediated VSMC stabilization.Conclusions These findings identify a gut microbiota-derived metabolite-driven signaling pathway that directly regulates VSMC phenotypic switching and atherosclerotic plaque stability in diabetes. The B. vulgatus/4MC/Notch axis represents a novel mechanistic link between intestinal dysbiosis and diabetic plaque vulnerability.",
  "authors": [
    {
      "affiliations": [
        "Shaanxi Provincial People’s Hospital, China"
      ],
      "name": "Zhongwei Liu"
    }
  ],
  "title": "IDDF2026-ABS-0034 Gut microbiota-derived bacteroides vulgatus regulates diabetic atherosclerotic plaque stability via the 4-methylcatechol-notch pathway",
  "uid": "7471e12f-03f9-5352-b9fc-78928879db4a"
}