肠道菌群参与异基因造血干细胞移植免疫重建调控的研究进展  

Gut microbiota modulates immune reconstitution in allogeneic hematopoietic stem cell transplantation

作　　者：陆海洋 赵维莅[1] 胡晓霞 LU Haiyang;ZHAO Weili;HU Xiaoxia(National Research Center for Translational Medicine at Shanghai,Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China)

机构地区：[1]上海交通大学医学院附属瑞金医院转化医学中心,上海200025

出　　处：《实用医学杂志》2025年第5期628-633,共6页The Journal of Practical Medicine

基　　金：国家重点研发计划(编号:2022YFC2502600);国家自然科学基金项目(编号:81710160,82170206);上海市“医苑新星”杰出青年医学人才培养计划(编号:20224Z0022)。

摘　　要：肠道菌群作为人体共生的微生物群体,其组成和功能影响人体代谢、免疫、内分泌等多方面生理功能。肠道菌群在异基因造血干细胞移植患者造血和免疫系统的精细调控上也发挥重要作用。在造血功能上,肠道菌群可以通过NOD1-STATs信号、TLRs-MyD88信号等通路调控造血干细胞向多谱系血细胞的分化,并在应激压力下推动造血干细胞向粒-单核系快速分化和成熟。因此,移植早期的原发性植入功能不良可能与肠道菌群功能紊乱有关。在免疫重建上,肠道菌群促进小肠上皮表达抗原递呈分子,是肠道aGVHD的重要始动因素。其次,肠道菌群可通过短链脂肪酸、胆汁酸、吲哚衍生物调节肠道免疫功能,其功能失调可导致肠道黏液屏障和免疫屏障功能紊乱,进一步促进肠道aGVHD发生和发展。因此,靶向肠道菌群成为一种有效的治疗策略,逐渐开始应用于临床。其中,粪便菌群移植联合传统抗排异治疗,可显著改善SR-aGVHD的临床严重程度和预后,其安全性高,不良反应可控,是SR-aGVHD治疗的新突破口。As a symbiotic microbial community within the human body,the gut microbiota plays a crucial role in modulating various physiological processes,including metabolism,immunity,and endocrine function.During allogeneic hematopoietic stem cell transplantation(allo-HSCT),the hematopoietic and immune systems undergo significant changes,which are also influenced by the gut microbiota.Specifically,regarding hematopoietic function,the gut microbiota facilitates the multi-lineage differentiation of hematopoietic stem cells via NOD1-STATs and TLRs-MyD88 signaling pathways,and promotes rapid granulomonocytic lineage differentiation under infection stress.Consequently,early-stage primary graft dysfunction following transplantation may be associated with gut microbiota dysbiosis.In terms of immune function,the gut microbiota enhances the expression of antigen-presenting molecules on intestinal epithelial cells,thereby initiating acute graft-versus-host disease(aGVHD)inthe gastrointestinal tract.Moreover,the gut microbiota regulates intestinal immune function through metabolites suchas short-chain fatty acids,bile acids,and indole derivatives.Dysbiosis of the gut microbiota can lead to disruptionof the intestinal mucus barrier and immune barrier functions,further promoting the onset and progression ofaGVHD in the gastrointestinal tract.Therefore,targeting the gut microbiota has emerged as an attractive therapeuticstrategy and has been clinically applied.Notably,fecal microbiota transplantation combined with immunosuppressivetherapy has shown significant efficacy in alleviating clinical severity and improving prognosis in steroid-refractoryaGVHD,demonstrating high safety and manageable adverse reactions,representing a novel breakthrough in itstreatment.

关 键 词：肠道菌群 异基因造血干细胞移植 免疫重建 移植物抗宿主病 移植物抗白血病效应 

分 类 号：R552[医药卫生—血液循环系统疾病]