Abstract

Antibody-mediated rejection (AMR) has become the major challenge for kidney transplantation, and the efficacy of existing therapies was limited to prevent AMR. Increasing evidences have demonstrated the link between gut microbiota alterations and allograft outcome. However, there has been no comprehensive analysis to profile the gut microbiota associated with AMR after kidney transplantation. We performed this study to characterize the gut microbiota possibly associated with AMR. Fecal specimens were collected from 24 kidney transplantation recipients with AMR and 29 controls. DNA extracted from the specimens was processed for 16S rRNA gene sequencing using Illumina MiSeq. Gut microbial community of recipients with AMR was significantly different from that of controls based on unweighted (P = 0.001) and weighted (P = 0.02) UniFrac distances, and the bacterial richness (observed species: P = 0.0448; Chao1 index: P = 0.0450; ACE index: P = 0.0331) significantly decreased in the AMR group. LEfSe showed that 1 phylum, 5 classes, 7 families, and 10 genera were increased, whereas 1 class, 2 order, 3 families, and 4 genera were decreased in the AMR group. Specific taxa such as Clostridiales could be potentially used as biomarkers to distinguish the recipients with AMR from the controls (AUC = 0.77). PICRUSt analysis illustrated that 16 functional pathways were with significantly different abundances in the AMR and control groups. Our findings provide a foundation for further investigation on the role of gut microbiota in AMR after kidney transplantation, and potentially support novel diagnostic biomarkers and therapeutic options for AMR.

Key points

• Gut microbial community of kidney recipients with AMR was different from that of controls.

• Clostridiales is a potential marker to distinguish recipients with AMR from controls.

中文翻译：

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肾脏移植后肠道微生物群改变与抗体介导的排斥反应有关

摘要

抗体介导的排斥反应（AMR）已成为肾脏移植的主要挑战，而现有疗法的疗效仅限于预防AMR。越来越多的证据表明肠道菌群改变与同种异体移植结果之间的联系。然而，还没有全面的分析来描述肾脏移植后与AMR相关的肠道菌群。我们进行了这项研究，以表征可能与AMR相关的肠道菌群。从24名接受AMR的肾脏移植受者和29名对照中收集粪便标本。使用Illumina MiSeq对从标本中提取的DNA进行16S rRNA基因测序。AMR受体的肠道微生物群落与未加权的对照组的肠道微生物群落显着不同（P =0.001）和加权（P = 0.02）UniFrac距离，以及细菌丰富度（观察物种：P = 0.0448； Chao1指数：P = 0.0450； ACE指数：P = 0.0331）在AMR组中显着降低。LEfSe显示，AMR组增加了1个门，5个类别，7个科和10个属，而减少了1个门，2个等级，3个科和4个属。特定分类群，如梭菌可能被用作生物标志物，以将接受AMR的接受者与对照组（AUC = 0.77）区分开。PICRUSt分析表明，AMR组和对照组中的16种功能途径的丰度明显不同。我们的发现为进一步研究肾脏微生物群在肾移植后在AMR中的作用提供了基础，并有可能支持AMR的新型诊断生物标志物和治疗选择。

关键点

•患有AMR的肾脏接受者的肠道微生物群落与对照组不同。

•梭菌是潜在的标志物，可将接受AMR的受检者与对照组区别开来。