Changes in Urinary Microbiome Populations Correlate in Kidney Transplants With Interstitial Fibrosis and Tubular Atrophy Documented in Early Surveillance Biopsies.
An unbalanced microbiome may lead to disease by creating aberrant immune responses. A recent association of cellular rejection with the development of interstitial fibrosis and tubular atrophy (IFTA) suggests the role of immune-mediated tissue injury. We hypothesized that developing IFTA correlates with altered urinary tract microbiomes (UMBs). UMBs at two serial time points, 1 and 6-8 months posttransplant, were assessed by 16S microbial ribosomal gene sequencing in 25 patients developing biopsy-proven IFTA compared to 23 transplant patients with normal biopsies and excellent function (TX) and 20 healthy nontransplant controls (HC). Streptococcus, the dominant genera in HC males, was lower in IFTA and TX males at 1 month compared to HCs. At 6-8 months, Streptococcus was further decreased in IFTA males, but normalized in TX. IFTA males and females had increases in number of genera per sample at 6-8 months. UMB composition varied substantially between individuals in all groups. Despite the wide variation in UMBs between individuals, IFTA was associated with a loss in dominant resident urinary microbes in males, and a parallel increase in nonresident, pathogenic bacteria in males and females. UMB changes may contribute to IFTA development by alteration of the host immune response.
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA.
B D
BD
Modena
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA.
R
R
Milam
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA.
F
F
Harrison
Department of Surgery, Duke University, Durham, NC.
J A
JA
Cheeseman
Northwestern Comprehensive Transplant Center, Northwestern University, Chicago, IL.
M M
0000-0001-9333-463X
MM
Abecassis
Northwestern Comprehensive Transplant Center, Northwestern University, Chicago, IL.
J J
0000-0002-9344-9928
JJ
Friedewald
Department of Surgery, Duke University, Durham, NC.
A D
AD
Kirk
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA.|DNA Microarray and Next Generation Sequencing Core, The Scripps Research Institute, La Jolla, CA.|Scripps Center for Organ Transplantation, Scripps Health, La Jolla, CA.
D R
DR
Salomon
D001284:Atrophy / Q000209:etiology / Q000652:urine*; D015415:Biomarkers / Q000652:urine*; D001706:Biopsy; D016022:Case-Control Studies; D005260:Female; D005355:Fibrosis / Q000209:etiology / Q000652:urine*; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000209:etiology / Q000473:pathology / Q000652:urine*; D006085:Graft Survival; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000601:surgery; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects*; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology*; D017563:Lung Diseases, Interstitial / Q000209:etiology / Q000652:urine*; D008297:Male; D064307:Microbiota / Q000235:genetics*; D008875:Middle Aged; D011379:Prognosis; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D012307:Risk Factors
D015415:Biomarkers; D012336:RNA, Ribosomal, 16S
basic (laboratory) research/science; clinical research/practice; immunobiology; immunosuppression/immune modulation; interstitial fibrosis and tubular atrophy; kidney (allograft) function/dysfunction; kidney transplantation/nephrology; microbiomics; rejection: chronic; tissue injury and repair