Approximately 33.6% of nondiabetic solid organ transplant recipients who received tacrolimus developed hyperglycemia. Whether the tacrolimus‐induced gut microbiota is involved in the regulation of hyperglycemia has not been reported. Hyperglycemia was observed in a tacrolimus‐treated mouse model, with reduction in taxonomic abundance of butyrate‐producing bacteria and decreased butyric acid concentration in the cecum. This tacrolimus‐induced glucose metabolic disorder was caused by the gut microbiota, as confirmed by a broad‐spectrum antibiotic model. Furthermore, oral supplementation with butyrate, whether for remedy or prevention, significantly increased the butyric acid content in the cecum and arrested hyperglycemia through the regulation of glucose‐regulating hormones, including glucagon‐like peptide‐1 (GLP‐1), peptide YY (PYY), and insulin, in serum. The butyrate–G‐protein‐coupled receptor 43–GLP‐1 pathway in the intestinal crypts may be involved in the pathogenesis of normalization of hyperglycemia caused by the tacrolimus. Therefore, tacrolimus affects glucose metabolism through the butyrate‐associated GLP‐1 pathway in the gut, and oral supplementation with butyrate provides new insights for the prevention and treatment of tacrolimus‐induced hyperglycemia in transplant recipients.

中文翻译：

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丁酸使由他克莫司诱导的肠道微生物群引起的高血糖正常化。

大约 33.6% 的接受他克莫司治疗的非糖尿病实体器官移植受者出现高血糖症。他克莫司诱导的肠道微生物群是否参与高血糖的调节尚未见报道。在他克莫司处理的小鼠模型中观察到高血糖症，其中产丁酸盐细菌的分类学丰度减少，盲肠中的丁酸浓度降低。正如广谱抗生素模型所证实的，这种他克莫司诱导的葡萄糖代谢紊乱是由肠道微生物群引起的。此外，口服丁酸盐补充剂，无论是治疗还是预防，都能显着增加盲肠中的丁酸含量，并通过调节葡萄糖调节激素（包括胰高血糖素样肽-1（GLP-1）、肽 YY）来抑制高血糖。 PYY）和胰岛素，在血清中。肠隐窝中的丁酸-G-蛋白偶联受体 43-GLP-1 通路可能参与了他克莫司引起的高血糖正常化的发病机制。因此，他克莫司通过肠道中丁酸相关的GLP-1通路影响葡萄糖代谢，口服补充丁酸为移植受者他克莫司诱导的高血糖症的预防和治疗提供了新的思路。