Lee John R, Muthukumar Thangamani, Dadhania Darshana, Toussaint Nora C, Ling Lilan, Pamer Eric, Suthanthiran Manikkam
1 Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medical College, New York, NY. 2 Department of Transplantation Medicine, New York Presbyterian Hospital-Weill Cornell Medical Center, New York, NY. 3 Infectious Diseases Services, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY. 4 Current address: New York Genome Center, New York, NY. 5 Address correspondence to: John Lee, M.D., Department of Medicine, Division of Nephrology and Hypertension 525 East 68th Street, Box 3, New York, NY 10065.
Transplantation. 2014 Oct 15;98(7):697-705. doi: 10.1097/TP.0000000000000370.
The gut microbiome plays a role in the regulation of the immune system.
We prospectively enrolled 26 kidney transplant recipients and collected serial fecal specimens (N=85) during the first three months of transplantation. We characterized bacterial composition by polymerase chain reaction amplification of the 16S rRNA V4-V5 variable region and deep sequencing using the Illumina MiSeq platform.
An increase in the relative abundance of Proteobacteria was observed in the posttransplantation specimens compared to pretransplantation specimens (P=0.04, Wilcoxon signed-rank test). In patients with posttransplant diarrhea, the mean(±standard deviation [SD]) Shannon diversity index was lower in those with diarrhea (N=6) than those without diarrhea (N=9) (2.5±0.3 vs. 3.4±0.8; P = 0.02, Wilcoxon rank-sum test). Principal coordinate analysis showed clear separation between the two groups, and linear discriminant analysis effect size (LEfSe) method revealed that Bacteroides, Ruminococcus, Coprococcus, and Dorea were significantly lower in the patients with diarrhea. Principal coordinate analysis also showed clear separation between the acute rejection (AR) group (N=3) and the no AR group (N=23) and the LEfSe method revealed significant differences between the two groups. Fecal abundance of Enterococcus was associated with Enterococcus urinary tract infection (UTI). The median Enterococcus fecal abundance was 24% (range, 8%-95%) in the three patients with Enterococcus UTI compared to 0% in the 23 patients without Enterococcus UTI (interquartile range, 0.00%-0.08%) (P=0.005, Wilcoxon rank-sum test).
Our pilot study identified significant alterations in the gut microbiota after kidney transplantation. Moreover, distinct microbiota structures were observed in allograft recipients with posttransplant diarrhea, AR, and Enterococcus UTI.
肠道微生物群在免疫系统调节中发挥作用。
我们前瞻性纳入了26名肾移植受者,并在移植后的前三个月收集了系列粪便标本(N = 85)。我们通过聚合酶链反应扩增16S rRNA V4-V5可变区并使用Illumina MiSeq平台进行深度测序来表征细菌组成。
与移植前标本相比,移植后标本中变形菌门的相对丰度增加(P = 0.04,Wilcoxon符号秩检验)。在移植后腹泻患者中,腹泻患者(N = 6)的平均(±标准差[SD])香农多样性指数低于无腹泻患者(N = 9)(2.5±0.3对3.4±0.8;P = 0.02,Wilcoxon秩和检验)。主坐标分析显示两组之间有明显分离,线性判别分析效应大小(LEfSe)方法显示腹泻患者中拟杆菌属、瘤胃球菌属、粪球菌属和多雷亚菌属显著降低。主坐标分析还显示急性排斥(AR)组(N = 3)和无AR组(N = 23)之间有明显分离,LEfSe方法显示两组之间存在显著差异。粪便中肠球菌的丰度与肠球菌尿路感染(UTI)相关。三名肠球菌UTI患者的粪便中肠球菌丰度中位数为24%(范围,8%-95%),而23名无肠球菌UTI患者的粪便中肠球菌丰度中位数为0%(四分位间距,0.00%-0.08%)(P = 0.005,Wilcoxon秩和检验)。
我们的初步研究发现肾移植后肠道微生物群有显著改变。此外,在移植后腹泻、AR和肠球菌UTI的同种异体移植受者中观察到不同的微生物群结构。