Frontiers of Medicine

, Volume 13, Issue 4, pp 471–481 | Cite as

Antibiotics-mediated intestinal microbiome perturbation aggravates tacrolimus-induced glucose disorders in mice

  • Yuqiu Han
  • Xiangyang Jiang
  • Qi Ling
  • Li Wu
  • Pin Wu
  • Ruiqi Tang
  • Xiaowei Xu
  • Meifang Yang
  • Lijiang Zhang
  • Weiwei Zhu
  • Baohong WangEmail author
  • Lanjuan Li
Research Article


Both immunosuppressants and antibiotics (ABX) are indispensable for transplant patients. However, the former increases the risk of new-onset diabetes, whereas the latter impacts intestinal microbiota (IM). It is still unclear whether and how the interaction between immunosuppressants and ABX alters the IM and thus leads to glucose metabolism disorders. This study examined the alterations of glucose and lipid metabolism and IM in mice exposed to tacrolimus (TAC) with or without ABX. We found that ABX further aggravated TAC-induced glucose tolerance and increased insulin secretion. Combined treatment resulted in exacerbated lipid accumulation in the liver. TAC-altered microbial community was further amplified by ABX administration, as characterized by reductions in phylum Firmicutes, family Lachnospiraceae, and genus Coprococcus. Analyses based on the metagenomic profiles revealed that ABX augmented the effect of TAC on microbial metabolic function mostly related to lipid metabolism. The altered components of gut microbiome and predicted microbial functional profiles showed significant correlation with hepatic lipid accumulation and glucose disorders. In conclusion, ABX aggravated the effect of TAC on the microbiome and its metabolic capacities, which might contribute to hepatic lipid accumulation and glucose disorders. These findings suggest that the ABX-altered microbiome can amplify the diabetogenic effect of TAC and could be a novel therapeutic target for patients.


antibiotics tacrolimus glucose disorders microbiome 


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This study was supported by the Science Fund for Distinguished Young Scholars of Zhejiang Provincial Natural Science Foundation of China (No. R16H260001) and Major Program of National Natural Science Foundation of China (Nos. 81790633 and 81790630). It also was supported by the Fundamental Research Funds for the Central Universities (No. 2018FZA7001). Lijiang Zhang received grants from the Science Technology Department of Zhejiang Province (No. 2014F30018). We thank Prof. Minli Chen and Mr. Lizong Zhang of Zhejiang Chinese Medical University for their help in the animal experiment and Dr. Honglei Weng of Heidelberg University for language improvement.

Supplementary material

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Supplementary material, approximately 153 KB.


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Copyright information

© Higher Education Press and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Yuqiu Han
    • 1
  • Xiangyang Jiang
    • 1
  • Qi Ling
    • 1
    • 2
  • Li Wu
    • 1
  • Pin Wu
    • 3
  • Ruiqi Tang
    • 1
  • Xiaowei Xu
    • 1
  • Meifang Yang
    • 1
  • Lijiang Zhang
    • 4
  • Weiwei Zhu
    • 1
  • Baohong Wang
    • 1
    Email author
  • Lanjuan Li
    • 1
  1. 1.National Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
  2. 2.Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, the First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
  3. 3.Division of Throat Surgery, the Second Affiliated HospitalZhejiang University School of MedicineHangzhouChina
  4. 4.Center of Safety EvaluationZhejiang Academy of Medical SciencesHangzhouChina

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