肠道微生物与肾移植术后 患者药物代谢及感染之间 的研究进展
Research Progress on the Relationship between Gut Microbiota and Drug Metabolism and Infections in Post-Kidney Transplant Patients
DOI: 10.12677/acm.2026.1662368, PDF,   
作者: 姜 和, 王建宁*:山东第一医科大学第一附属医院泌尿外科,山东 济南
关键词: 肠道微生物肾移植感染他克莫司免疫抑制Gut Microbiota Kidney Transplantation Infection Tacrolimus Immunosuppression
摘要: 肾移植受者由于长期接受免疫抑制治疗,成为术后感染的严重高危人群。近年来,肠道微生物群作为人体重要的“虚拟器官”,其与免疫系统功能和全身性疾病的关联日益受到关注。本综述旨在探讨肠道微生物群在肾移植受者术后免疫状态调节中的作用,以及肾移植术后他克莫司药物浓度是如何影响肠道菌群。并深入分析其与移植术后患者感染的严重程度及预后的潜在关联。并展望以肠道微生物为靶点的潜在干预策略,为改善肾移植术后感染者的临床管理提供新视角,以及通过改善肠道微生态,辅助他克莫司实现更平稳的血药浓度,减少毒副作用并且提高疗效。
Abstract: Kidney transplant recipients, due to long-term immunosuppressive therapy, become a high-risk group for postoperative infections. In recent years, the gut microbiota, as an important “virtual organ” of the human body, has increasingly received attention for its association with immune system function and systemic diseases. This review aims to explore the role of the gut microbiota in regulating the immune status of kidney transplant recipients after surgery, as well as how postoperative tacrolimus drug levels affect the gut microbiome. It further analyzes the potential correlation between the gut microbiota and the severity and prognosis of infections in post-transplant patients. Moreover, it looks forward to potential intervention strategies targeting the gut microbiota, providing new perspectives for improving the clinical management of postoperative infections in kidney transplant patients, and assisting tacrolimus in achieving more stable blood concentrations, reducing toxic side effects, and enhancing efficacy through the improvement of gut microbial ecology.
文章引用:姜和, 王建宁. 肠道微生物与肾移植术后 患者药物代谢及感染之间 的研究进展[J]. 临床医学进展, 2026, 16(6): 1541-1549. https://doi.org/10.12677/acm.2026.1662368

参考文献

[1] Wekerle, T., Segev, D., Lechler, R. and Oberbauer, R. (2017) Strategies for Long-Term Preservation of Kidney Graft Function. The Lancet, 389, 2152-2162. [Google Scholar] [CrossRef] [PubMed]
[2] Rinninella, E., Raoul, P., Cintoni, M., Franceschi, F., Miggiano, G.A.D., Gasbarrini, A., et al. (2019) What Is the Healthy Gut Microbiota Composition? A Changing Ecosystem across Age, Environment, Diet, and Diseases. Microorganisms, 7, 14. [Google Scholar] [CrossRef] [PubMed]
[3] Davenport, E.R., Sanders, J.G., Song, S.J., Amato, K.R., Clark, A.G. and Knight, R. (2017) The Human Microbiome in Evolution. BMC Biology, 15, Article No. 127. [Google Scholar] [CrossRef] [PubMed]
[4] Dominguez-Bello, M.G., Godoy-Vitorino, F., Knight, R. and Blaser, M.J. (2019) Role of the Microbiome in Human Development. Gut, 68, 1108-1114. [Google Scholar] [CrossRef] [PubMed]
[5] Tabibian, J.H. and Kenderian, S.S. (2017) The Microbiome and Immune Regulation after Transplantation. Transplantation, 101, 56-62. [Google Scholar] [CrossRef] [PubMed]
[6] Sivaraj, S., Chan, A., Pasini, E., Chen, E., Lawendy, B., Verna, E., et al. (2020) Enteric Dysbiosis in Liver and Kidney Transplant Recipients: A Systematic Review. Transplant International, 33, 1163-1176. [Google Scholar] [CrossRef] [PubMed]
[7] De Keyzer, K., Van Laecke, S., Peeters, P. and Vanholder, R. (2011) Human Cytomegalovirus and Kidney Transplantation: A Clinician’s Update. American Journal of Kidney Diseases, 58, 118-126. [Google Scholar] [CrossRef] [PubMed]
[8] Przybyciński, J., Drożdżal, S., Wilk, A., Dziedziejko, V., Szumilas, K. and Pawlik, A. (2023) The Effect of the Gut Microbiota on Transplanted Kidney Function. International Journal of Molecular Sciences, 24, Article 1260. [Google Scholar] [CrossRef] [PubMed]
[9] Yu, D.H., Ying, N., Lian, Z.H. and Fa, Y.Q. (2021) The Alteration Human of Gut Microbiota and Metabolites before and after Renal Transplantation. Microbial Pathogenesis, 160, Article 105191. [Google Scholar] [CrossRef] [PubMed]
[10] Taur, Y., Xavier, J.B., Lipuma, L., Ubeda, C., Goldberg, J., Gobourne, A., et al. (2012) Intestinal Domination and the Risk of Bacteremia in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation. Clinical Infectious Diseases, 55, 905-914. [Google Scholar] [CrossRef] [PubMed]
[11] Swarte, J.C., Li, Y., Hu, S., Björk, J.R., Gacesa, R., Vich Vila, A., et al. (2022) Gut Microbiome Dysbiosis Is Associated with Increased Mortality after Solid Organ Transplantation. Science Translational Medicine, 14, eabn7566. [Google Scholar] [CrossRef] [PubMed]
[12] Gabarre, P., Loens, C., Tamzali, Y., Barrou, B., Jaisser, F. and Tourret, J. (2022) Immunosuppressive Therapy after Solid Organ Transplantation and the Gut Microbiota: Bidirectional Interactions with Clinical Consequences. American Journal of Transplantation, 22, 1014-1030. [Google Scholar] [CrossRef] [PubMed]
[13] Li, H. and Jia, W. (2013) Cometabolism of Microbes and Host: Implications for Drug Metabolism and Drug-Induced Toxicity. Clinical Pharmacology & Therapeutics, 94, 574-581. [Google Scholar] [CrossRef] [PubMed]
[14] Haiser, H.J. and Turnbaugh, P.J. (2012) Is It Time for a Metagenomic Basis of Therapeutics? Science, 336, 1253-1255. [Google Scholar] [CrossRef] [PubMed]
[15] Lee, J.R., Muthukumar, T., Dadhania, D., Taur, Y., Jenq, R.R., Toussaint, N.C., et al. (2015) Gut Microbiota and Tacrolimus Dosing in Kidney Transplantation. PLOS ONE, 10, e0122399. [Google Scholar] [CrossRef] [PubMed]
[16] Ardalan, M. and Vahed, S.Z. (2017) Gut Microbiota and Renal Transplant Outcome. Biomedicine & Pharmacotherapy, 90, 229-236. [Google Scholar] [CrossRef] [PubMed]
[17] Ding, D. (2010) Post-Kidney Transplant Rejection and Infection Complications. Nephrology Nursing Journal, 37, 419-426.
[18] Zhang, L.T., Westblade, L.F., Iqbal, F., Taylor, M.R., Chung, A., Satlin, M.J., et al. (2021) Gut Microbiota Profiles and Fecal Beta-Glucuronidase Activity in Kidney Transplant Recipients with and without Post-Transplant Diarrhea. Clinical Transplantation, 35, e14260. [Google Scholar] [CrossRef] [PubMed]
[19] Bunnapradist, S., Lentine, K.L., Burroughs, T.E., Pinsky, B.W., Hardinger, K.L., Brennan, D.C., et al. (2006) Mycophenolate Mofetil Dose Reductions and Discontinuations after Gastrointestinal Complications Are Associated with Renal Transplant Graft Failure. Transplantation, 82, 102-107. [Google Scholar] [CrossRef] [PubMed]
[20] Ye, J., Yao, J., He, F., Sun, J., Zhao, Z. and Wang, Y. (2023) Regulation of Gut Microbiota: A Novel Pretreatment for Complications in Patients Who Have Undergone Kidney Transplantation. Frontiers in Cellular and Infection Microbiology, 13, Article 1169500. [Google Scholar] [CrossRef] [PubMed]
[21] Fishman, J.A. (2007) Infection in Solid-Organ Transplant Recipients. New England Journal of Medicine, 357, 2601-2614. [Google Scholar] [CrossRef] [PubMed]
[22] Agrawal, A., Ison, M.G. and Danziger-Isakov, L. (2022) Long-Term Infectious Complications of Kidney Transplantation. Clinical Journal of the American Society of Nephrology, 17, 286-295. [Google Scholar] [CrossRef] [PubMed]
[23] Lee, J.R., Muthukumar, T., Dadhania, D., Toussaint, N.C., Ling, L., Pamer, E., et al. (2014) Gut Microbial Community Structure and Complications after Kidney Transplantation: A Pilot Study. Transplantation, 98, 697-705. [Google Scholar] [CrossRef] [PubMed]
[24] Fricke, W.F., Maddox, C., Song, Y. and Bromberg, J.S. (2014) Human Microbiota Characterization in the Course of Renal Transplantation. American Journal of Transplantation, 14, 416-427. [Google Scholar] [CrossRef] [PubMed]
[25] Wang, J., Li, X., Wu, X., Wang, Z., Zhang, C., Cao, G., et al. (2021) Gut Microbiota Alterations Associated with Antibody-Mediated Rejection after Kidney Transplantation. Applied Microbiology and Biotechnology, 105, 2473-2484. [Google Scholar] [CrossRef] [PubMed]
[26] DeGruttola, A.K., Low, D., Mizoguchi, A. and Mizoguchi, E. (2016) Current Understanding of Dysbiosis in Disease in Human and Animal Models. Inflammatory Bowel Diseases, 22, 1137-1150. [Google Scholar] [CrossRef] [PubMed]
[27] Rossi, M., Johnson, D.W., Morrison, M., Pascoe, E.M., Coombes, J.S., Forbes, J.M., et al. (2016) Synbiotics Easing Renal Failure by Improving Gut Microbiology (SYNERGY): A Randomized Trial. Clinical Journal of the American Society of Nephrology, 11, 223-231. [Google Scholar] [CrossRef] [PubMed]
[28] Gorres, K.L., Daigle, D., Mohanram, S. and Miller, G. (2014) Activation and Repression of Epstein-Barr Virus and Kaposi’s Sarcoma-Associated Herpesvirus Lytic Cycles by Short-and Medium-Chain Fatty Acids. Journal of Virology, 88, 8028-8044. [Google Scholar] [CrossRef] [PubMed]
[29] Conti, C., Malacrino, C. and Mastromarino, P. (2009) Inhibition of Herpes Simplex Virus Type 2 by Vaginal Lactobacilli. Journal of Physiology and Pharmacology, 60, 19-26.
[30] Mastromarino, P., Cacciotti, F., Masci, A. and Mosca, L. (2011) Antiviral Activity of Lactobacillus Brevis towards Herpes Simplex Virus Type 2: Role of Cell Wall Associated Components. Anaerobe, 17, 334-336. [Google Scholar] [CrossRef] [PubMed]
[31] Chan, S., Isbel, N.M., Hawley, C.M., Campbell, S.B., Campbell, K.L., Morrison, M., et al. (2019) Infectious Complications Following Kidney Transplantation—A Focus on Hepatitis C Infection, Cytomegalovirus Infection and Novel Developments in the Gut Microbiota. Medicina, 55, Article 672. [Google Scholar] [CrossRef] [PubMed]
[32] Sawas, T., Al Halabi, S., Hernaez, R., Carey, W.D. and Cho, W.K. (2015) Patients Receiving Prebiotics and Probiotics before Liver Transplantation Develop Fewer Infections than Controls: A Systematic Review and Meta-Analysis. Clinical Gastroenterology and Hepatology, 13, 1567-1574.e3. [Google Scholar] [CrossRef] [PubMed]
[33] Bellini, A., Finocchietti, M., Rosa, A.C., Nordio, M., Ferroni, E., Massari, M., et al. (2024) Effectiveness and Safety of Immunosuppressive Regimens Used as Maintenance Therapy in Kidney Transplantation: The CESIT Study. PLOS ONE, 19, e0295205. [Google Scholar] [CrossRef] [PubMed]
[34] Toral, M., Romero, M., Rodríguez-Nogales, A., Jiménez, R., Robles-Vera, I., Algieri, F., et al. (2018) Lactobacillus fermentum Improves Tacrolimus-Induced Hypertension by Restoring Vascular Redox State and Improving Enos Coupling. Molecular Nutrition & Food Research, 62, Article 1800033. [Google Scholar] [CrossRef] [PubMed]
[35] Zheng, Y.P., Masand, A., Wagner, M., Kapur, S., Dadhania, D., Lubetzky, M., et al. (2019) Identification of Antibiotic Administration as a Potentially Novel Factor Associated with Tacrolimus Trough Variability in Kidney Transplant Recipients: A Preliminary Study. Transplantation Direct, 5, e485. [Google Scholar] [CrossRef] [PubMed]
[36] Nakamura, A., Amada, N., Haga, I., Tokodai, K. and Kashiwadate, T. (2014) Effects of Elevated Tacrolimus Trough Levels in Association with Infectious Enteritis on Graft Function in Renal Transplant Recipients. Transplantation Proceedings, 46, 592-594. [Google Scholar] [CrossRef] [PubMed]
[37] Dukaew, N., Noppakun, K., Thongkumkoon, P., Na Takuathung, M., Inpan, R., Kongta, N., et al. (2025) Associations between the Gut Microbiota and the Metabolism Rate of Tacrolimus in Kidney Transplant Recipients during the Early Posttransplant Period. Archives of Pharmacal Research, 48, 549-562. [Google Scholar] [CrossRef] [PubMed]
[38] Gentile, C.L. and Weir, T.L. (2018) The Gut Microbiota at the Intersection of Diet and Human Health. Science, 362, 776-780. [Google Scholar] [CrossRef] [PubMed]
[39] Davani-Davari, D., Negahdaripour, M., Karimzadeh, I., Seifan, M., Mohkam, M., Masoumi, S., et al. (2019) Prebiotics: Definition, Types, Sources, Mechanisms, and Clinical Applications. Foods, 8, Article 92. [Google Scholar] [CrossRef] [PubMed]
[40] Bromberg, J.S., Fricke, W.F., Brinkman, C.C., Simon, T. and Mongodin, E.F. (2015) Microbiota—Implications for Immunity and Transplantation. Nature Reviews Nephrology, 11, 342-353. [Google Scholar] [CrossRef] [PubMed]
[41] Arpaia, N., Campbell, C., Fan, X., Dikiy, S., van der Veeken, J., deRoos, P., et al. (2013) Metabolites Produced by Commensal Bacteria Promote Peripheral Regulatory T-Cell Generation. Nature, 504, 451-455. [Google Scholar] [CrossRef] [PubMed]
[42] Artis, D. (2008) Epithelial-cell Recognition of Commensal Bacteria and Maintenance of Immune Homeostasis in the Gut. Nature Reviews Immunology, 8, 411-420. [Google Scholar] [CrossRef] [PubMed]
[43] Kamada, N., Chen, G.Y., Inohara, N. and Núñez, G. (2013) Control of Pathogens and Pathobionts by the Gut Microbiota. Nature Immunology, 14, 685-690. [Google Scholar] [CrossRef] [PubMed]
[44] Revolinski, S.L. and Munoz-Price, L.S. (2019) Clostridioides Difficile in Transplant Patients: Early Diagnosis, Treatment, and Prevention. Current Opinion in Infectious Diseases, 32, 307-313. [Google Scholar] [CrossRef] [PubMed]
[45] Winichakoon, P., Chaiwarith, R., Chattipakorn, N. and Chattipakorn, S.C. (2022) Impact of Gut Microbiota on Kidney Transplantation. Transplantation Reviews, 36, Article 100668. [Google Scholar] [CrossRef] [PubMed]