Intestinal microbiota-derived metabolomic blood plasma markers for prior radiation injury.
Intestinal microbiota-derived metabolomic blood plasma markers for prior radiation injury.
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肠道菌群衍生的代谢组血浆标志物，用于先前的辐射损伤。
DOI：
10.1016/j.ijrobp.2014.10.023
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发表时间：
2015-02-01
影响因子：
7
通讯作者：
Golden, Aaron
中科院分区：
文献类型：
--
作者：
Broin, Pilib O.;Vaitheesvaran, Bhavapriya;Saha, Subhrajit;Hartil, Kirsten;Chen, Emily I.;Goldman, Devorah;Fleming, William Harv;Kurland, Irwin J.;Guha, Chandan;Golden, Aaron
评估全身辐射损伤和吸收剂量对于在医疗、工业、军事或恐怖事件中意外或故意暴露后的补救工作至关重要。我们假设，从血浆中提取的特定代谢物浓度的变化将与全身辐射损伤和剂量相关。C57BL/6小鼠随机分为6组，每组12只，分别接受0Gy2Gy4Gy8Gy10.4Gy5次γ全身照射。在治疗后24小时，所有动物都被安乐死，并获得血浆和肝脏活检-后者被用来消除血浆中明显的肝脏辐射损伤反应。使用GC/MS和LC/MS/MS平台进行了半定量的非靶向代谢物/脂谱分析，鉴定了354种生物化学物质。第二组C57BL/6小鼠(每组6只)被用来评估超过24小时的已识别血浆标志物的子集。我们确定了血浆中37种生化化合物的队列，这些化合物产生了辐照样本组的最佳分离，其中相关性最强的代谢物与嘧啶(正相关)和色氨酸(负相关)代谢有关。后者主要与吲哚类化合物有关，有证据表明，这些也与肝脏和血浆有关。没有观察到饱和作为剂量的函数的证据，这已经在涉及尿液代谢物分析的研究中被注意到。与嘧啶和色氨酸途径相关的特定代谢物的血浆图谱可用于区分全身辐射损伤和剂量反应。由于色氨酸相关的吲哚化合物起源于肠道微生物组，然后是肝脏，这些代谢物特别代表了血浆中辐射损伤的一个有吸引力的标志。
Assessing whole-body radiation injury and absorbed dose is essential for remediation efforts following accidental or deliberate exposure in medical, industrial, military, or terrorist incidents. We hypothesize that variations in specific metabolite concentrations extracted from blood plasma would correlate with whole-body radiation injury and dose. Groups of C57BL/6 mice (n=12 per group) were exposed to 0 Gy, 2 Gy, 4 Gy, 8 Gy, and 10.4 Gy of whole-body γ-radiation. At 24 hours post treatment all animals were euthanized and both plasma and liver biopsies obtained - the latter being used to deconvolve a distinct hepatic radiation injury response within plasma. A semi-quantitative untargeted metabolites/lipid profiling using both GC/MS and LC/MS/MS platforms was performed and identified 354 biochemicals. A second set of C57BL/6 mice (n=6 per group) were used to assess a subset of identified plasma markers beyond 24 hours. We identified a cohort of 37 biochemical compounds in plasma that yielded the optimal separation of the irradiated sample groups, with the most correlated metabolites associated with pyrimidine (positively correlated) and tryptophan (negatively correlated) metabolism. The latter were predominantly associated with indole compounds, and there was evidence to indicate that these were also correlated between liver and plasma. No evidence of saturation as a function of dose was observed, as has been noted for studies involving metabolite analysis of urine. Plasma profiling of specific metabolites related to the pyrimidine and tryptophan pathways can be used to differentiate whole-body radiation injury and dose response. As the tryptophan associated indole compounds have their origin in the intestinal microbiome and subsequently the liver, these metabolites in particular represent an attractive marker for radiation injury within blood plasma.
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影响因子：
3.6
作者：
Liu, Yue;Lin, Ze-Bin;Chai, Yi-Feng
通讯作者：
Chai, Yi-Feng
影响因子：
3.4
作者：
ONOUE, M;UCHIDA, K;MUTAI, M
通讯作者：
MUTAI, M
影响因子：
3.4
作者：
POLLARD, EC;LYDERSEN, BK
通讯作者：
LYDERSEN, BK
DOI：
10.1073/pnas.0504830102
发表时间：
2005-09-13
影响因子：
11.1
作者：
Crawford, PA;Gordon, JI
通讯作者：
Gordon, JI
影响因子：
3.4
作者：
Johnson CH;Patterson AD;Krausz KW;Lanz C;Kang DW;Luecke H;Gonzalez FJ;Idle JR
通讯作者：
Idle JR