Gut microbiota and tacrolimus dosing in kidney transplantation Journal Article


Authors: Lee, J. R.; Muthukumar, T.; Dadhania, D.; Taur, Y.; Jenq, R. R.; Toussaint, N. C.; Ling, L.; Pamer, E.; Suthanthiran, M.
Article Title: Gut microbiota and tacrolimus dosing in kidney transplantation
Abstract: Tacrolimus dosing to establish therapeutic levels in recipients of organ transplants is a challenging task because of much interpatient and intrapatient variability in drug absorption, metabolism, and disposition. In view of the reported impact of gut microbial species on drug metabolism, we investigated the relationship between the gut microbiota and tacrolimus dosing requirements in this pilot study of adult kidney transplant recipients. Serial fecal specimens were collected during the first month of transplantation from 19 kidney transplant recipients who either required a 50% increase from initial tacrolimus dosing during the first month of transplantation (Dose Escalation Group, n=5) or did not require such an increase (Dose Stable Group, n=14). We characterized bacterial composition in the fecal specimens by deep sequencing of the PCR amplified 16S rRNA V4-V5 region and we investigated the hypothesis that gut microbial composition is associated with tacrolimus dosing requirements. Initial tacrolimus dosing was similar in the Dose Escalation Group and in the Stable Group (4.2±1.1 mg/day vs. 3.8±0.8 mg/day, respectively, P=0.61, two-way betweengroup ANOVA using contrasts) but became higher in the Dose Escalation Group than in the Dose Stable Group by the end of the first transplantation month (9.6±2.4 mg/day vs. 3.3±1.5 mg/day, respectively, P<0.001). Our systematic characterization of the gut microbial composition identified that fecal Faecalibacterium prausnitzii abundance in the first week of transplantation was 11.8% in the Dose Escalation Group and 0.8% in the Dose Stable Group (P=0.002, Wilcoxon Rank Sum test, P<0.05 after Benjamini-Hochberg correction for multiple hypotheses). Fecal Faecalibacterium prausnitzii abundance in the first week of transplantation was positively correlated with future tacrolimus dosing at 1 month (R=0.57, P=0.01) and had a coefficient±standard error of 1.0±0.6 (P=0.08) after multivariable linear regression. Our novel observations may help further explain inter-individual differences in tacrolimus dosing to achieve therapeutic levels. © 2015 Lee et al.
Keywords: adult; clinical article; controlled study; prednisone; dose response; polymerase chain reaction; cohort analysis; body weight; hemoglobin; bacteria (microorganisms); age; alanine aminotransferase; albumin; pilot study; living donor; drug metabolism; drug dose increase; intestine flora; gender; immunosuppressive treatment; tacrolimus; rna 16s; african american; graft recipient; feces analysis; rna sequence; kidney graft rejection; kidney transplantation; steroid therapy; microbial diversity; thrush; mycophenolic acid; clotrimazole; kidney donor; human; male; female; article; population abundance; faecalibacterium prausnitzii; rna deep sequencing
Journal Title: PLoS ONE
Volume: 10
Issue: 3
ISSN: 1932-6203
Publisher: Public Library of Science  
Date Published: 2015-03-27
Start Page: e0122399
Language: English
DOI: 10.1371/journal.pone.0122399
PROVIDER: scopus
PMCID: PMC4376942
PUBMED: 25815766
DOI/URL:
Notes: Export Date: 3 June 2015 -- Source: Scopus
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MSK Authors
  1. Eric Pamer
    266 Pamer
  2. Robert R Jenq
    103 Jenq
  3. Ying Taur
    101 Taur
  4. Lilan Ling
    40 Ling