Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China.
Am J Transplant. 2018 Jul;18(7):1646-1656. doi: 10.1111/ajt.14661. Epub 2018 Feb 3.
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 CD25 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.
环孢素诱导的肠道微生物群改变可能影响免疫功能和器官移植。用高剂量环孢素处理小鼠 14 天。通过焦磷酸测序 16S rRNA 基因分析粪便微生物群，并使用序列数据预测对代谢的影响。通过流式细胞术确定血清、肠道相关淋巴组织和引流淋巴结中的 T 细胞亚群。环孢素治疗显著改变了结肠黏膜和循环中 Allobaculum、拟杆菌和乳杆菌以及 CD4 CD25 FoxP3 调节性 T 细胞的相对丰度。在接受环孢素治疗或来自接受环孢素治疗的供体的粪便微生物群转移治疗后，这些都显著增加。此外，在皮肤移植模型中，低剂量环孢素加来自高剂量环孢素改变的小鼠的粪便微生物群转移治疗增加了皮肤移植物的存活率。因此，高剂量环孢素改变了肠道微生物群的组成和分类群。施用这些调理肠道微生物群加低剂量环孢素导致结肠和全身免疫反应的调节以及移植物存活率的增加。这项研究通过将免疫抑制剂与肠道微生物群移植相结合，为控制移植物排斥提供了一种新策略。
