John R Lee1, Thangamani Muthukumar, Darshana Dadhania, Nora C Toussaint, Lilan Ling, Eric Pamer, Manikkam Suthanthiran. 1. 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.
Abstract
BACKGROUND: The gut microbiome plays a role in the regulation of the immune system. METHODS: 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. RESULTS: 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). CONCLUSION: 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.
BACKGROUND: The gut microbiome plays a role in the regulation of the immune system. METHODS: 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. RESULTS: 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). CONCLUSION: 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.
Authors: Suphamai Bunnapradist; Krista L Lentine; Thomas E Burroughs; Brett W Pinsky; Karen L Hardinger; Daniel C Brennan; Mark A Schnitzler Journal: Transplantation Date: 2006-07-15 Impact factor: 4.939
Authors: Suphamai Bunnapradist; Luca Neri; Wendy Wong; Krista L Lentine; Thomas E Burroughs; Brett W Pinsky; Steven K Takemoto; Mark A Schnitzler Journal: Am J Kidney Dis Date: 2008-03 Impact factor: 8.860
Authors: Lorraine C Racusen; Robert B Colvin; Kim Solez; Michael J Mihatsch; Philip F Halloran; Patricia M Campbell; Michael J Cecka; Jean-Pierre Cosyns; Anthony J Demetris; Michael C Fishbein; Agnes Fogo; Peter Furness; Ian W Gibson; Denis Glotz; Pekka Hayry; Lawrence Hunsickern; Michael Kashgarian; Ronald Kerman; Alex J Magil; Robert Montgomery; Kunio Morozumi; Volker Nickeleit; Parmjeet Randhawa; Heinz Regele; Daniel Seron; Surya Seshan; Stale Sund; Kiril Trpkov Journal: Am J Transplant Date: 2003-06 Impact factor: 8.086
Authors: Elmar Pruesse; Christian Quast; Katrin Knittel; Bernhard M Fuchs; Wolfgang Ludwig; Jörg Peplies; Frank Oliver Glöckner Journal: Nucleic Acids Res Date: 2007-10-18 Impact factor: 16.971
Authors: Joseph A Spinner; Claire E Bocchini; Ruth A Luna; Santosh Thapa; Miriam A Balderas; Susan W Denfield; William J Dreyer; Dorottya Nagy-Szakal; Faith D Ihekweazu; James Versalovic; Tor Savidge; Richard Kellermayer Journal: Pediatr Transplant Date: 2019-10-16
Authors: Franco B Mueller; Hua Yang; Michelle Lubetzky; Akanksha Verma; John R Lee; Darshana M Dadhania; Jenny Z Xiang; Steven P Salvatore; Surya V Seshan; Vijay K Sharma; Olivier Elemento; Manikkam Suthanthiran; Thangamani Muthukumar Journal: JCI Insight Date: 2019-07-11
Authors: Jonathan S Bromberg; Lauren Hittle; Yanbao Xiong; Vikas Saxena; Eoghan M Smyth; Lushen Li; Tianshu Zhang; Chelsea Wagner; W Florian Fricke; Thomas Simon; Colin C Brinkman; Emmanuel F Mongodin Journal: JCI Insight Date: 2018-10-04