Tao Yan-Xin, Zhang Er-Di, Yue Jia-Xi, Wan Zheng-Li, Fan Ji-Wen, Li Yi, Fan Yu, Yan Lin
Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China.
Sichuan Clinical Research Center for Laboratory Medicine, Chengdu, China.
BMC Microbiol. 2025 Jul 31;25(1):468. doi: 10.1186/s12866-025-04103-3.
Kidney transplantation is currently the most effective method for treating end-stage renal disease. However, postoperative-related rejection and IgA nephropathy remains a serious obstacle to the long-term survival of kidney transplant patients. Its pathogenesis is not fully understood, and potential causative factors remain to be explored. In this study, we used 2bRAD-M to analyze differences in the peripheral blood microbiome of renal transplant recipients who were stable postoperatively (STABLE) and those who developed chronic antibody-mediated rejection (CAMR) or IgA nephropathy (IgAN) recurrence.
Thirty one renal transplant patients were recruited, including 12 STABLE, 8 CAMR and 11 IgAN patients after kidney transplantation. 2bRAD-M was used to characterize the microbiota in peripheral blood to explore the presence of microbial differences.
Differences in microbial community composition were observed between CAMR, IgAN and STABLE. The alpha diversity of CAMR and IgAN was all higher than STABLE, there are also differences in beta diversity. LEfSe was performed to identify different abundance taxa, 21 discriminative features between CAMR and STABLE, 39 discriminative features between IgAN and STABLE. The mean decrease Gini index and random forest analysis indicated that Staphylococcus_epidermidis might serve as indicator bacteria for CAMR, Kocuria_palustris might serve as indicator bacteria for IgAN. ROC analysis was performed to assess the performance of some optimal marker models, and the average AUC value achieved 89.6% between CAMR and STABLE, 67.4% between IgAN and STABLE. Functional annotation analysis showed 4353 different COGs and 378 related signaling pathways between CAMR and STABLE, 4396 different COGs and 384 related signaling pathways between CAMR and STABLE.
The first 2bRAD-M microbiome study of CAMR and IgAN after renal transplantation showed a potential association between the circulating microbiome and the disease, and provided a possible target and basis for subsequent studies of the mechanisms underlying the development and progression of CAMR and IgAN after renal transplantation.
肾移植是目前治疗终末期肾病最有效的方法。然而,术后相关排斥反应和IgA肾病仍然是肾移植患者长期生存的严重障碍。其发病机制尚未完全明确,潜在致病因素仍有待探索。在本研究中,我们使用2bRAD-M分析术后病情稳定的肾移植受者(STABLE组)与发生慢性抗体介导排斥反应(CAMR)或IgA肾病(IgAN)复发的受者外周血微生物组的差异。
招募31例肾移植患者,包括12例术后病情稳定者、8例发生慢性抗体介导排斥反应者和11例IgA肾病复发者。使用2bRAD-M对外周血中的微生物群进行特征分析,以探索微生物差异的存在。
观察到CAMR组、IgAN组和STABLE组之间微生物群落组成存在差异。CAMR组和IgAN组的α多样性均高于STABLE组,β多样性也存在差异。进行线性判别分析效应大小(LEfSe)以识别不同丰度的分类群,CAMR组和STABLE组之间有21个判别特征,IgAN组和STABLE组之间有39个判别特征。平均减少基尼指数和随机森林分析表明,表皮葡萄球菌可能是CAMR的指示菌,沼泽考克氏菌可能是IgAN的指示菌。进行ROC分析以评估一些最佳标志物模型的性能,CAMR组和STABLE组之间的平均AUC值达到89.6%,IgAN组和STABLE组之间为67.4%。功能注释分析显示,CAMR组和STABLE组之间有4353个不同的同源基因簇(COG)和378条相关信号通路,IgAN组和STABLE组之间有4396个不同的COG和384条相关信号通路。
首次对肾移植后CAMR和IgAN进行的2bRAD-M微生物组研究显示循环微生物组与疾病之间存在潜在关联,并为后续研究肾移植后CAMR和IgAN发生发展机制提供了可能的靶点和依据。