Gut microbiota and tacrolimus dosing in kidney transplantation.
Gut microbiota and tacrolimus dosing in kidney transplantation.
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DOI：
10.1371/journal.pone.0122399
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Suthanthiran M
中科院分区：
文献类型：
--
作者：
Lee JR;Muthukumar T;Dadhania D;Taur Y;Jenq RR;Toussaint NC;Ling L;Pamer E;Suthanthiran M
由于患者之间和患者内部的药物吸收、代谢和处置存在很大差异，因此在器官移植受者中确定他克莫司剂量以确定治疗水平是一项具有挑战性的任务。鉴于已报道的肠道微生物种类对药物代谢的影响，我们在这项针对成人肾移植受者的初步研究中研究了肠道微生物群与他克莫司剂量要求之间的关系。在移植第一个月期间从 19 名肾移植受者处收集了连续粪便样本，这些受者在移植第一个月期间需要比初始他克莫司剂量增加 50%（剂量递增组，n=5）或不需要这样的增加（剂量稳定组，n=14）。我们通过对 PCR 扩增的 16S rRNA V4-V5 区域进行深度测序来表征粪便样本中的细菌组成，并研究了肠道微生物组成与他克莫司剂量要求相关的假设。剂量递增组和稳定组的初始他克莫司剂量相似（分别为 4.2±1.1 毫克/天与 3.8±0.8 毫克/天，P=0.61，使用对比的双向组间方差分析），但在第一个移植月末，剂量递增组的剂量高于剂量稳定组（9.6±2.4 毫克/天与 3.8±0.8 毫克/天）。分别为3.3±1.5毫克/天，P<0.001）。我们对肠道微生物组成的系统表征发现，移植第一周粪便中普拉梭菌丰度在剂量递增组中为 11.8%，在剂量稳定组中为 0.8%（P=0.002，Wilcoxon 秩和检验，在对多个假设进行 Benjamini-Hochberg 校正后 P<0.05）。移植第一周粪便中普拉梭菌丰度与未来 1 个月他克莫司剂量呈正相关（R=0.57，P=0.01），多变量线性回归后系数±标准误为 1.0±0.6（P=0.08）。我们的新观察结果可能有助于进一步解释达到治疗水平的他克莫司剂量的个体差异。
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 between-group 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.
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DOI：
10.1038/ismej.2012.8
发表时间：
2012-08
期刊：
The ISME journal
影响因子：
--
作者：
通讯作者：
--
影响因子：
6.2
作者：
Jacobson PA;Oetting WS;Brearley AM;Leduc R;Guan W;Schladt D;Matas AJ;Lamba V;Julian BA;Mannon RB;Israni A;DeKAF Investigators
通讯作者：
DeKAF Investigators
影响因子：
2.9
作者：
Page, RL;Klem, PM;Rogers, C
通讯作者：
Rogers, C
影响因子：
1.3
作者：
Maezono, S;Sugimoto, K;Fujimura, A
通讯作者：
Fujimura, A
影响因子：
12.2
作者：
Flint HJ;Scott KP;Duncan SH;Louis P;Forano E
通讯作者：
Forano E