Statins are currently the most common cholesterol-lowering drug, but the underlying mechanism of statin-induced hyperglycemia is unclear. To investigate whether the gut microbiome and its metabolites contribute to statin-associated glucose intolerance, we recruited 30 patients with atorvastatin and 10 controls, followed up for 16 weeks, and found a decreased abundance of the genus in feces and altered serum and fecal bile acid profiles among patients with atorvastatin therapy. Animal experiments validated that statin could induce glucose intolerance, and transplantation of and supplementation of ursodeoxycholic acid (UDCA) could ameliorate statin-induced glucose intolerance. Furthermore, oral UDCA administration in humans alleviated the glucose intolerance without impairing the lipid-lowering effect. Our study demonstrated that the statin-induced hyperglycemic effect was attributed to the -bile acids axis and provided important insights into adjuvant therapy of UDCA to lower the adverse risk of statin therapy.

中文翻译：

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他汀类药物通过以微生物群依赖性方式降低血液胰高血糖素样肽 1 水平来加剧胰岛素抵抗

他汀类药物是目前最常见的降胆固醇药物，但他汀类药物引起高血糖的潜在机制尚不清楚。为了研究肠道微生物组及其代谢物是否会导致他汀类药物相关的葡萄糖不耐受，我们招募了 30 名服用阿托伐他汀的患者和 10 名对照者，随访 16 周，发现粪便中该属的丰度降低，血清和粪便胆汁酸发生改变阿托伐他汀治疗患者的概况。动物实验证实他汀类药物可引起葡萄糖不耐受，移植和补充熊去氧胆酸（UDCA）可改善他汀类药物引起的葡萄糖不耐受。此外，人类口服UDCA可缓解葡萄糖不耐受，但不会损害降脂作用。我们的研究表明，他汀类药物引起的高血糖效应归因于β-胆汁酸轴，并为UDCA辅助治疗降低他汀类药物治疗的不良风险提供了重要见解。