TY - JOUR
T1 - Butyric acid normalizes hyperglycemia caused by the tacrolimus-induced gut microbiota
AU - Jiao, Wenjiao
AU - Zhang, Zijian
AU - Xu, Yue
AU - Gong, Lian
AU - Zhang, Weixun
AU - Tang, Hao
AU - Zeng, Song
AU - Zhang, Qiang
AU - Sun, Zhaoli
AU - Liu, Ling
AU - Hu, Xiaopeng
N1 - Funding Information:
This work was supported by The General Program of National Natural Science Foundation of China (NSFC) (81670679, 81970463 and 81970645). The joint fund of Beijing Municipal Commission of Education and Natural Science Foundation of Beijing Municipality (KZ202010025036).
Funding Information:
This work was supported by The General Program of National Natural Science Foundation of China (NSFC) (81670679 & 81970463). The joint fund of Beijing Municipal Commission of Education and Natural Science Foundation of Beijing Municipality (KZ202010025036).
Publisher Copyright:
© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons
PY - 2020/9/1
Y1 - 2020/9/1
N2 - 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.
AB - 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.
KW - basic (laboratory) research/science
KW - complication: medical/metabolic
KW - diabetes: new onset/posttransplant
KW - drug toxicity
KW - endocrinology/diabetology
KW - immunosuppressant - calcineurin inhibitor: tacrolimus
KW - immunosuppression/immune modulation
KW - microbiomics
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U2 - 10.1111/ajt.15880
DO - 10.1111/ajt.15880
M3 - Article
C2 - 32243709
AN - SCOPUS:85085152560
SN - 1600-6135
VL - 20
SP - 2413
EP - 2424
JO - American Journal of Transplantation
JF - American Journal of Transplantation
IS - 9
ER -