期刊
AMERICAN JOURNAL OF TRANSPLANTATION
卷 18, 期 7, 页码 1646-1656出版社
WILEY
DOI: 10.1111/ajt.14661
关键词
basic (laboratory) research; science; immunosuppressant - calcineurin inhibitor: tacrolimus; immunosuppression; immune modulation; metabolism; metabolite; organ transplantation in general; rejection: acute
资金
- National Natural Science Foundation of China [81270837, 81670679]
The alterations induced in gut microbiota by tacrolimus may affect immune function and organ transplantation. Mice were treated with high-dose tacrolimus for 14days. 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(+)CD25(hi)FoxP3(+) 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. In a mouse model, gut microbiome transplantation plus low-dose tacrolimus results in the suppression of colonic and systemic immune responses and an increased allograft survival rate.
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