Wang Zijie, Gao Xiang, Ji Hongsheng, Shao Ming, Ni Bin, Fei Shuang, Sun Li, Chen Hao, Tan Ruoyun, Du Mulong, Gu Min
Department of Urology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210003, China.
Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
J Transl Med. 2025 Apr 10;23(1):420. doi: 10.1186/s12967-025-06090-5.
The gut-lung-kidney axis is pivotal in immune-related kidney diseases, with gut dysbiosis potentially exacerbating the severity of Coronavirus disease 2019 (COVID-19) in recipients of kidney transplant. This study aimed to characterize the gut microbiome and metabolome in renal transplant recipients with COVID-19 pneumonia over a one-year follow-up period.
A total of 30 renal transplant recipients were enrolled, comprising 17 with COVID-19 pneumonia, six with mild COVID-19, and seven without COVID-19. Fecal samples were collected at the onset of infection for gut microbiome and metabolome analysis. Generalized Estimating Equations (GEE) model and Latent Class Growth Mixed Model (LCGMM) were employed to dissect the relationships among clinical characteristics, laboratory tests, and gut microbiota and metabolites.
Four microbial phyla (Deferribacteres, TM7, Fusobacteria, and Gemmatimonadetes) and 13 genera were significantly enriched across three recipients groups, correlating with baseline inflammatory response and allograft function. Additionally, 52 differentially expressed metabolites were identified, with seven significantly correlating with eight altered microbiota genera. LCGMM revealed two distinct classes of recipients, with those suffering from COVID-19 pneumonia exhibiting significantly elevated serum creatinine (Scr) trajectories over the one-year period. GEE further identified 12 genera and 181 metabolites closely associated with these trajectories; a multivariable model incorporating gut metabolites of 1-Caffeoylquinic Acid and PMK was found to effectively predict one-year allograft function.
Our study indicates a possible interaction between the composition of the gut microbiota and metabolites community and COVID-19 in renal transplant recipients, particularly in relation to disease severity and the prediction of one-year allograft function.
肠-肺-肾轴在免疫相关性肾脏疾病中起关键作用，肠道菌群失调可能会加重肾移植受者的2019冠状病毒病（COVID-19）病情。本研究旨在对肾移植受者合并COVID-19肺炎患者进行为期一年的随访，以表征其肠道微生物组和代谢组。
共纳入30名肾移植受者，其中17名合并COVID-19肺炎，6名患轻度COVID-19，7名未感染COVID-19。在感染发作时采集粪便样本，进行肠道微生物组和代谢组分析。采用广义估计方程（GEE）模型和潜在类别增长混合模型（LCGMM）来剖析临床特征、实验室检查与肠道微生物群及代谢物之间的关系。
在三个受者组中，四个微生物门（脱铁杆菌门、TM7、梭杆菌门和芽单胞菌门）和13个属显著富集，与基线炎症反应和移植肾功能相关。此外，鉴定出52种差异表达的代谢物，其中7种与8个改变的微生物属显著相关。LCGMM揭示了两类不同的受者，合并COVID-19肺炎的受者在一年期间血清肌酐（Scr）轨迹显著升高。GEE进一步确定了与这些轨迹密切相关的12个属和181种代谢物；发现一个包含1-咖啡酰奎尼酸和PMK肠道代谢物的多变量模型可有效预测一年的移植肾功能。
我们的研究表明，肾移植受者肠道微生物群和代谢物群落组成与COVID-19之间可能存在相互作用，特别是在疾病严重程度和一年移植肾功能预测方面。
