Gut microbiota and tacrolimus dosing in kidney transplantation

John R. Lee, Thangamani Muthukumar, Darshana Dadhania, Ying Taur, Robert R. Jenq, Nora C. Toussaint, Lilan Ling, Eric Pamer, Manikkam Suthanthiran

Research output: Contribution to journalArticle

36 Citations (Scopus)

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.

Original languageEnglish
Article numbere0122399
JournalPLoS One
Volume10
Issue number3
DOIs
Publication statusPublished - 27 Mar 2015
Externally publishedYes

Fingerprint

tacrolimus
kidney transplant
Tacrolimus
intestinal microorganisms
Kidney Transplantation
Transplants
dosage
Transplantation
feces composition
Nonparametric Statistics
Metabolism
pharmacokinetics
Chemical analysis
Transplantation (surgical)
organ transplantation
High-Throughput Nucleotide Sequencing
therapeutics
Analysis of variance (ANOVA)
Gastrointestinal Microbiome
Linear regression

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Lee, J. R., Muthukumar, T., Dadhania, D., Taur, Y., Jenq, R. R., Toussaint, N. C., ... Suthanthiran, M. (2015). Gut microbiota and tacrolimus dosing in kidney transplantation. PLoS One, 10(3), [e0122399]. https://doi.org/10.1371/journal.pone.0122399

Gut microbiota and tacrolimus dosing in kidney transplantation. / Lee, John R.; Muthukumar, Thangamani; Dadhania, Darshana; Taur, Ying; Jenq, Robert R.; Toussaint, Nora C.; Ling, Lilan; Pamer, Eric; Suthanthiran, Manikkam.

In: PLoS One, Vol. 10, No. 3, e0122399, 27.03.2015.

Research output: Contribution to journalArticle

Lee, JR, Muthukumar, T, Dadhania, D, Taur, Y, Jenq, RR, Toussaint, NC, Ling, L, Pamer, E & Suthanthiran, M 2015, 'Gut microbiota and tacrolimus dosing in kidney transplantation', PLoS One, vol. 10, no. 3, e0122399. https://doi.org/10.1371/journal.pone.0122399
Lee JR, Muthukumar T, Dadhania D, Taur Y, Jenq RR, Toussaint NC et al. Gut microbiota and tacrolimus dosing in kidney transplantation. PLoS One. 2015 Mar 27;10(3). e0122399. https://doi.org/10.1371/journal.pone.0122399
Lee, John R. ; Muthukumar, Thangamani ; Dadhania, Darshana ; Taur, Ying ; Jenq, Robert R. ; Toussaint, Nora C. ; Ling, Lilan ; Pamer, Eric ; Suthanthiran, Manikkam. / Gut microbiota and tacrolimus dosing in kidney transplantation. In: PLoS One. 2015 ; Vol. 10, No. 3.
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