Urinary microbiome of kidney transplant patients reveals dysbiosis with potential for antibiotic resistance

Abstract

Recent studies have established that a complex community of microbes colonize the human urinary tract; however their role in kidney transplant patients treated with prophylactic antibiotics remains poorly investigated. Our aim was to investigate the urinary microbiome of kidney transplant recipients. Urine samples from 21 patients following kidney transplantation and 8 healthy controls, were collected. All patients received prophylactic treatment with the antibiotic trimethoprim/sulfamethoxazole. Metagenomic DNA was isolated from urine samples, sequenced using metagenomics shotgun sequencing approach on Illumina HiSeq2000 platform, and analyzed for microbial taxonomic and functional annotations. Our results demonstrate that the urine microbiome of kidney transplants was markedly different at all taxonomic levels from phyla to species, had decreased microbial diversity and increased abundance of potentially pathogenic species compared to healthy controls. Specifically, at the phylum level we detected a significant decrease in Actinobacteria and increase in Firmicutes due to increases in Enterococcus faecalis. In addition, there was an increase in the Proteobacteria due to increases in E. coli. Analysis of predicted functions of the urinary metagenome revealed increased abundance of enzymes in the folate pathway including dihydrofolate synthase that are not inhibited by trimethoprim/ sulfamethoxazole, but can augment folate metabolism. This report characterizes the urinary microbiome of kidney transplants using shotgun metagenomics approach. Our results indicate that the urinary microbiota may be modified in the context of prophylactic antibiotics, indicating that a therapeutic intervention may shift the urinary microbiota to select bacterial species with increased

Evaluating bacterial and functional diversity of human gut microbiota by complementary metagenomics and metatranscriptomics

“…10). This implies that the identified functions are similar in either the read or contig 5 based analysis of the MT data with slight variations. 6 We investigated the MG and MT data at the species level.…”

“…1C and1D). To evaluate technical reproducibility, we 5 constructed 12 unique indexed metatranscriptome libraries from a single fecal sample. High quality libraries 6 were prepared for sequencing on Illumina's MiSeq and HiSeq 2000 platforms ( Supplementary Fig.…”

Impact of environmental factors on alloimmunity and transplant fate

“…Many factors could theoretically have an effect on microbial composition after transplantation, including administration of prophylactic antibiotics or antivirals, administration of immunosuppressive drugs, the initial graft damage from IRI, and the alloimmune response to the transplanted organ. Regardless of the cause, shifts in bacterial communities have been repeatedly reported in fecal, oral, or urine samples of transplant hosts (119)(120)(121)(122)(123)(124), most often involving loss of microbial diversity.…”

Urinary microbiome associated with chronic allograft dysfunction in kidney transplant recipients

“…Alterations in the urinary microbiome have been explored in a variety of lower urinary tract disorders such as urinary incontinence, interstitial cystitis, urologic cancers, and chronic prostatitis, but little is yet known about urinary microbiome alterations in renal allograft dysfunction. Quantification of the urinary microbiome in renal allograft recipients has been performed in small cohorts, and dysregulation of the microbiome has been associated with interstitial fibrosis and tubular atrophy (IFTA) . However, to our knowledge, the urinary microbiome has not been studied in CAD prior to IFTA development.…”

“…Quantification of the urinary microbiome in renal allograft recipients has been performed in small cohorts, 14,15 and dysregulation of the microbiome has been associated with interstitial fibrosis and tubular atrophy (IFTA). 16 However, to our knowledge, the urinary microbiome has not been studied in CAD prior to IFTA development.…”