Integrative metagenomic and metabolomic analyses reveal the role of gut microbiota in antibody-mediated renal allograft rejection.
Integrative metagenomic and metabolomic analyses reveal the role of gut microbiota in antibody-mediated renal allograft rejection.
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DOI：
10.1186/s12967-022-03825-6
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发表时间：
2022-12-23
影响因子：
7.4
通讯作者：
Yan, Tianzhong
中科院分区：
文献类型：
--
作者：
Li, Xin;Li, Ruoying;Ji, Bingqing;Zhao, Lili;Wang, Junpeng;Yan, Tianzhong
抗体介导的排斥反应（Antibody-mediated rejection，AMR）是肾移植术后移植肾存活的主要障碍之一。我们之前的研究表明，AMR肾移植受者的肠道微生物群失调。然而，在物种水平上的肠道微生物功能和结构的变化尚未确定。在本研究中，我们研究了AMR患者肠道微生物群的宏基因组和代谢模式，以全面深入地了解AMR患者肠道微生物群生态失调。我们招募了60名肾移植受者，其中28名显示AMR，32名为移植后肾功能稳定的非AMR对照。在AMR肾移植受者和对照组中进行粪便样本的鸟枪测序和非靶向LC/MS代谢组学分析。总共，我们鉴定了311种下调和27种上调的与肾移植后AMR相关的肠道微生物物种，导致22条途径中富集的437个基因的表达水平改变，其中13个与代谢相关。此外，在AMR受者中发现了32种差异粪便代谢物。其中，3b-羟基-5-胆烯酸、l-哌啶酸、牛磺胆酸和6 k-PGF 1 α-d4的改变与肠道微生物种类和功能的变化直接相关。特异性差异粪便种类和代谢物与临床指标（Cr、BUN等）密切相关，并且可以作为潜在的生物标志物区分AMR受体和对照。总之，我们的研究结果提供了一个全面和深入的了解AMR和肠道菌群之间的相关性，这是重要的肾移植后AMR的病因学和诊断研究。在线版本包含补充材料，可通过10.1186/s12967-022-03825-6获得。
Antibody-mediated rejection (AMR) remains one of the major barriers for graft survival after kidney transplantation. Our previous study suggested a gut microbiota dysbiosis in kidney transplantation recipients with AMR. However, alternations in gut microbial function and structure at species level have not been identified. In the present study, we investigated the metagenomic and metabolic patterns of gut microbiota in AMR patients to provide a comprehensive and in-depth understanding of gut microbiota dysbiosis in AMR. We enrolled 60 kidney transplantation recipients, 28 showed AMR and 32 were non-AMR controls with stable post-transplant renal functions. Shotgun sequencing and untargeted LC/MS metabolomic profiling of fecal samples were performed in kidney transplantation recipients with AMR and controls. Totally, we identified 311 down-regulated and 27 up-regulated gut microbial species associated with AMR after kidney transplantation, resulting in the altered expression levels of 437 genes enriched in 22 pathways, of which 13 were related to metabolism. Moreover, 32 differential fecal metabolites were found in recipients with AMR. Among them, alterations in 3b-hydroxy-5-cholenoic acid, l-pipecolic acid, taurocholate, and 6k-PGF1alpha-d4 directly correlated with changes in gut microbial species and functions. Specific differential fecal species and metabolites were strongly associated with clinical indexes (Cr, BUN, etc.), and could distinguish the recipients with AMR from controls as potential biomarkers. Altogether, our findings provided a comprehensive and in-depth understanding of the correlation between AMR and gut microbiota, which is important for the etiological and diagnostic study of AMR after kidney transplantation. The online version contains supplementary material available at 10.1186/s12967-022-03825-6.
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影响因子：
8.8
作者：
Matas, A. J.;Smith, J. M.;Kasiske, B. L.
通讯作者：
Kasiske, B. L.
影响因子：
48
作者：
Huan T;Forsberg EM;Rinehart D;Johnson CH;Ivanisevic J;Benton HP;Fang M;Aisporna A;Hilmers B;Poole FL;Thorgersen MP;Adams MWW;Krantz G;Fields MW;Robbins PD;Niedernhofer LJ;Ideker T;Majumder EL;Wall JD;Rattray NJW;Goodacre R;Lairson LL;Siuzdak G
通讯作者：
Siuzdak G
DOI：
10.3390/ani10091588
发表时间：
2020-09-06
期刊：
Animals : an open access journal from MDPI
影响因子：
--
作者：
Alaqil AA;Abbas AO;El-Beltagi HS;El-Atty HKA;Mehaisen GMK;Moustafa ES
通讯作者：
Moustafa ES
DOI：
10.1093/bioinformatics/bts565
发表时间：
2012-12-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Fu L;Niu B;Zhu Z;Wu S;Li W
通讯作者：
Li W
影响因子：
3.6
作者：
Lu, Haifeng;He, Jianqing;Li, Lanjuan
通讯作者：
Li, Lanjuan