Immunosuppressive effect of the gut microbiome altered by high-dose tacrolimus in mice

Z. Zhang, L. Liu, H. Tang, W. Jiao, S. Zeng, Y. Xu, Q. Zhang, Z. Sun, A. Mukherjee, X. Zhang, X. Hu

Research output: Contribution to journalArticle

Abstract

The alterations induced in gut microbiota by tacrolimus may affect immune function and organ transplantation. Mice were treated with high-dose tacrolimus for 14 days. The fecal microbiota were analyzed by pyrosequencing the 16S rRNA genes, and the effect on metabolism was predicted using the sequence data. The subgroups of T cells in the serum, gut-associated lymphoid tissue, and draining lymph nodes were determined by flow cytometry. Tacrolimus treatment significantly altered the relative abundance of Allobaculum, Bacteroides, and Lactobacillus and CD4+CD25hiFoxP3+ regulatory T cells in the colonic mucosa and the circulation. These were significantly increased after either tacrolimus treatment or treatment by fecal microbiota transfer from tacrolimus-treated donors. Further, treatment with low-dose tacrolimus plus fecal microbiota transfer from high-dose tacrolimus–altered mice increased skin allograft survival rate in a skin transplantation model. Thus, high-dose tacrolimus alters the compositions and taxa of the gut microbiota. Administration of these conditioned gut microbiota plus low-dose tacrolimus resulted in regulation of colonic and systemic immune responses and an increased allograft survival rate. This study demonstrated a new strategy for controlling allograft rejection by combining an immunosuppressive agent with gut microbiome transplantation.

Original languageEnglish (US)
Pages (from-to)1646-1656
Number of pages11
JournalAmerican Journal of Transplantation
Volume18
Issue number7
DOIs
StatePublished - Jul 2018

Keywords

  • basic (laboratory) research/science
  • immunosuppressant - calcineurin inhibitor: tacrolimus
  • immunosuppression/immune modulation
  • metabolism/metabolite
  • organ transplantation in general
  • rejection: acute

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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  • Cite this

    Zhang, Z., Liu, L., Tang, H., Jiao, W., Zeng, S., Xu, Y., Zhang, Q., Sun, Z., Mukherjee, A., Zhang, X., & Hu, X. (2018). Immunosuppressive effect of the gut microbiome altered by high-dose tacrolimus in mice. American Journal of Transplantation, 18(7), 1646-1656. https://doi.org/10.1111/ajt.14661