Butyric acid normalizes hyperglycemia caused by the tacrolimus-induced gut microbiota

Wenjiao Jiao, Zijian Zhang, Yue Xu, Lian Gong, Weixun Zhang, Hao Tang, Song Zeng, Qiang Zhang, Zhaoli Sun, Ling Liu, Xiaopeng Hu

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)2413-2424
Number of pages12
JournalAmerican Journal of Transplantation
Volume20
Issue number9
DOIs
StatePublished - Sep 1 2020

Keywords

  • basic (laboratory) research/science
  • complication: medical/metabolic
  • diabetes: new onset/posttransplant
  • drug toxicity
  • endocrinology/diabetology
  • immunosuppressant - calcineurin inhibitor: tacrolimus
  • immunosuppression/immune modulation
  • microbiomics

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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