Gut Microbiota and Metabolite Changes Induced by Tacrolimus: Implications for Skin Transplant Immunology in Mice
Year: 2025
Type: article
Abstract: 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 workCorrespondence: Xin Li, Email [email protected] Ming Zhao, Email [email protected]: 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
Authors: Wang J, Zhang X, Cui C, Li M, Xie Z, Yang L, Ding D, Li X, Zhao M
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7087863987
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