目的 探讨粪菌移植（fecal microbiota transplantation, FMT）改善小鼠异基因造血干细胞移植（allogeneic hematopoietic stem cell transplantation, allo⁃HSCT）后急性移植物抗宿主病（acute graft⁃versus⁃host disease, aGVHD）胃肠道炎症反应的分子机制。 方法 建立小鼠aGVHD模型，将BALB/c小鼠随机分为空白对照组、骨髓移植组、aGVHD模型组、FMT治疗组，每组6只。通过组织病理学检查观察各组小鼠组织病理学损伤情况，采用免疫组织化学检测受体相互作用蛋白激酶（receptor⁃interacting protein kinase, RIPK）1、RIPK3、混合谱系激酶结构域样蛋白（mixed lineage kinase domain⁃like protein, MLKL）表达，Western blot法检测RIPK1、RIPK3、MLKL、磷酸化RIPK1（phosphorylated RIPK1, p⁃RIPK1）、磷酸化MLKL（phosphorylated MLKL, p⁃MLKL）蛋白表达水平，酶联免疫吸附试验检测血浆中再生胰岛衍生蛋白3α（regenerating islet⁃derived protein 3 alpha, Reg3α）含量。通过16S rRNA基因测序对肠道菌群进行分析。 结果 与aGVHD模型组相比，FMT治疗组厚壁菌门、拟杆菌门相对丰度升高，变形菌门相对丰度降低；小鼠体重下降趋势明显缓解，死亡发生时间延缓。与aGVHD模型组相比，FMT治疗组α多样性指数（Simpson, Pielou, Shannon）升高（P<0.05），肠道病理评分和RIPK1、RIPK3、MLKL表达及RIPK1、RIPK3、MLKL、p⁃RIPK1、p⁃MLKL蛋白表达水平、血浆Reg3α水平显著降低（P<0.05）。 结论 FMT可能通过重建肠道菌群平衡，抑制RIPK1/RIPK3介导的坏死性凋亡通路，减轻aGVHD胃肠道炎症反应。

Objective To investigate the molecular mechanism by which fecal microbiota transplantation (FMT) alleviates gastrointestinal inflammation after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in murine acute graft-versus-host disease (aGVHD). Methods A murine aGVHD model after allo-HSCT was established, and BALB/c mice were randomly assigned to blank control, bone marrow transplantation, aGVHD model, and FMT treatment groups (n=6 per group). Disease severity was assessed by histopathology. Expression of receptor-interacting protein kinase (RIPK)1, RIPK3, and mixed lineage kinase domain-like protein (MLKL) was evaluated by immunohistochemistry. Protein levels of RIPK1, RIPK3, MLKL, phosphorylated RIPK1 (p-RIPK1), and phosphorylated MLKL (p-MLKL) were determined by Western blotting. Plasma regenerating islet-derived protein 3 alpha (Reg3α) was measured by enzyme-linked immunosorbent assay. The intestinal microbiota was profiled by 16S rRNA gene sequencing. Results Compared with the aGVHD model group, the FMT group showed higher relative abundances of Firmicutes and Bacteroidetes and a lower relative abundance of Proteobacteria; body weight loss was markedly attenuated, and survival time was prolonged. Alpha-diversity indices (Simpson, Pielou, Shannon) increased in the FMT group (P<0.05). Intestinal pathology scores, expression of RIPK1, RIPK3, and MLKL, protein levels of RIPK1, RIPK3, MLKL, p-RIPK1, and p-MLKL, and plasma Reg3α levels were significantly reduced in the FMT group versus the aGVHD model group (all P<0.05). Conclusions FMT may attenuate gastrointestinal inflammation in aGVHD by restoring intestinal microbial balance and inhibiting the RIPK1/RIPK3-mediated necroptosis pathway.