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已发表论文
他克莫司诱导的小鼠肠道菌群及代谢物变化：对皮肤移植免疫学的影响
Authors Wang J, Zhang X, Cui C, Li M, Xie Z, Yang L, Ding D, Li X , Zhao M
Received 9 May 2025
Accepted for publication 30 September 2025
Published 9 October 2025 Volume 2025:18 Pages 14059—14073
DOI https://doi.org/10.2147/JIR.S539452
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Tara Strutt
Junpeng Wang,1,* Xiaofan Zhang,2,* Cuiyun Cui,3 Mengjun Li,4 Zixuan Xie,4 Lei Yang,5 Degang Ding,1 Xin Li,4 Ming Zhao6
1Department of Urology, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Zhengzhou, People’s Republic of China; 2Medical Discipline and Research Office, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 3Department of Blood Transfusion, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Zhengzhou, People’s Republic of China; 4Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, People’s Republic of China; 5Department of Pathology, Yale University, New Haven, CT, USA; 6Department of Organ Transplantation, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Xin Li, Email lixin0930@zzu.edu.cn Ming Zhao, Email zhaoming02@hotmail.com
Background: Tacrolimus is the most widely used immunosuppressive therapy in solid organ transplantation. However, whether it can inhibit transplant graft rejection by altering the composition and metabolism of gut microbiota remains unclear.
Methods: In this study, a skin transplantation mouse model was established to explore the effects of tacrolimus on gut microbiota and its metabolites. Additionally, we investigated the protective effect and potential mechanism of feces from mice treated with tacrolimus on skin allografts.
Results: Tacrolimus did not significantly affect gut microbiota α-diversity but altered β-diversity, with specific changes in microbial composition. LEfSe analysis identified 19 microbial taxa with reduced and 12 with elevated relative abundance in the Tac group (mice treated with tacrolimus) compared to the Ctrl group (mice with no treatment). Metabolomic analysis identified 33 differential fecal metabolites (17 upregulated and 16 downregulated) in the Tac group compared to the Ctrl group. FMT from tacrolimus-treated mice significantly prolonged skin allograft survival, reduced inflammatory cell infiltration, and improved graft histopathology. This protective effect was associated with increased Treg cell proportions and decreased Th17 cell proportions in draining lymph nodes and mesenteric lymph node.
Conclusion: Overall, our data may provide a basis for establishing gut microbiota-based therapies for allograft rejection.
Keywords: graft rejection, transplantation, intestinal flora, tacrolimus, intestinal metabolic profile
1Department of Urology, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Zhengzhou, People’s Republic of China; 2Medical Discipline and Research Office, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 3Department of Blood Transfusion, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Zhengzhou, People’s Republic of China; 4Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, People’s Republic of China; 5Department of Pathology, Yale University, New Haven, CT, USA; 6Department of Organ Transplantation, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Xin Li, Email lixin0930@zzu.edu.cn Ming Zhao, Email zhaoming02@hotmail.com
Background: Tacrolimus is the most widely used immunosuppressive therapy in solid organ transplantation. However, whether it can inhibit transplant graft rejection by altering the composition and metabolism of gut microbiota remains unclear.
Methods: In this study, a skin transplantation mouse model was established to explore the effects of tacrolimus on gut microbiota and its metabolites. Additionally, we investigated the protective effect and potential mechanism of feces from mice treated with tacrolimus on skin allografts.
Results: Tacrolimus did not significantly affect gut microbiota α-diversity but altered β-diversity, with specific changes in microbial composition. LEfSe analysis identified 19 microbial taxa with reduced and 12 with elevated relative abundance in the Tac group (mice treated with tacrolimus) compared to the Ctrl group (mice with no treatment). Metabolomic analysis identified 33 differential fecal metabolites (17 upregulated and 16 downregulated) in the Tac group compared to the Ctrl group. FMT from tacrolimus-treated mice significantly prolonged skin allograft survival, reduced inflammatory cell infiltration, and improved graft histopathology. This protective effect was associated with increased Treg cell proportions and decreased Th17 cell proportions in draining lymph nodes and mesenteric lymph node.
Conclusion: Overall, our data may provide a basis for establishing gut microbiota-based therapies for allograft rejection.
Keywords: graft rejection, transplantation, intestinal flora, tacrolimus, intestinal metabolic profile