Butyric acid normalizes hyperglycemia caused by the tacrolimus‐induced gut microbiota. Issue 9 (8th May 2020)

• Record Type: Journal Article
• Authors: Jiao, Wenjiao; Zhang, Zijian; Xu, Yue; Gong, Lian; Zhang, Weixun; Tang, Hao; Zeng, Song; Zhang, Qiang; Sun, Zhaoli; Liu, Ling; Hu, Xiaopeng
• Is Part Of: American journal of transplantation. Volume 20:Issue 9(2020)
• Page Start: 2413
• Page End: 2424
• Publication Date: 2020-05-08
• Subjects: basic (laboratory) research/science -- complication: medical/metabolic -- diabetes: new onset/posttransplant -- drug toxicity -- endocrinology/diabetology -- immunosuppressant ‐ calcineurin inhibitor: tacrolimus -- immunosuppression/immune modulation -- microbiomics; Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.15880
• Languages: English
• ISSNs: 1600-6135

Abstract

Abstract : 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. Abstract : This study finds a new pathogenic mechanism of tacrolimus‐induced hyperglycemia with reduction in the taxonomic abundance of butyrate‐producing bacteria and decreased butyric acid concentration in the cecum, which is restored by oral butyrate supplementation.