Gut microbiota dysbiosis and diarrhea in kidney transplant recipients

John Richard Lee, Matthew Magruder, Lisa Zhang, Lars F. Westblade, Michael J. Satlin, Amy Robertson, Emmanuel Edusei, Carl Crawford, Lilan Ling, Ying Taur, Jonas Schluter, Michelle Lubetzky, Darshana Dadhania, Eric Pamer, Manikkam Suthanthiran

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10 Citations (Scopus)

Abstract

Posttransplant diarrhea is associated with kidney allograft failure and death, but its etiology remains unknown in the majority of cases. Because altered gut microbial ecology is a potential basis for diarrhea, we investigated whether posttransplant diarrhea is associated with gut dysbiosis. We enrolled 71 kidney allograft recipients for serial fecal specimen collections in the first 3 months of transplantation and profiled the gut microbiota using 16S ribosomal RNA (rRNA) gene V4-V5 deep sequencing. The Shannon diversity index was significantly lower in 28 diarrheal fecal specimens from 25 recipients with posttransplant diarrhea than in 112 fecal specimens from 46 recipients without posttransplant diarrhea. We found a lower relative abundance of 13 commensal genera (Benjamini-Hochberg adjusted P ≤ .15) in the diarrheal fecal specimens including the same 4 genera identified in our prior study. The 28 diarrheal fecal specimens were also evaluated by a multiplexed polymerase chain reaction (PCR) assay for 22 bacterial, viral, and protozoan gastrointestinal pathogens, and 26 specimens were negative for infectious etiologies. Using PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) to predict metagenomic functions, we found that diarrheal fecal specimens had a lower abundance of metabolic genes. Our findings suggest that posttransplant diarrhea is not associated with common infectious diarrheal pathogens but with a gut dysbiosis.

Original languageEnglish
JournalAmerican Journal of Transplantation
DOIs
Publication statusAccepted/In press - 1 Jan 2018

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Keywords

  • Complication: medical/metabolic
  • Diarrhea
  • Gut microbiota
  • Kidney disease
  • Kidney transplantation/nephrology
  • Microbiomics
  • Translational research/science

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

Cite this

Lee, J. R., Magruder, M., Zhang, L., Westblade, L. F., Satlin, M. J., Robertson, A., Edusei, E., Crawford, C., Ling, L., Taur, Y., Schluter, J., Lubetzky, M., Dadhania, D., Pamer, E., & Suthanthiran, M. (Accepted/In press). Gut microbiota dysbiosis and diarrhea in kidney transplant recipients. American Journal of Transplantation. https://doi.org/10.1111/ajt.14974