Targeted LC-MS/MS profiling of bile acids reveals primary/secondary bile acid ratio as a novel biomarker for necrotizing enterocolitis.
Targeted LC-MS/MS profiling of bile acids reveals primary/secondary bile acid ratio as a novel biomarker for necrotizing enterocolitis.
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DOI：
10.1007/s00216-023-05017-7
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发表时间：
2024-01
影响因子：
4.3
通讯作者：
Lu, Li
中科院分区：
文献类型：
--
作者：
Gao, Tingting;Hu, Shaohua;Xu, Weijue;Wang, Zhiru;Guo, Ting;Chen, Feng;Ma, Yingxuan;Zhu, Linlin;Chen, Faling;Wang, Xiaomei;Zhou, Jin;Lv, Zhibao;Lu, Li
关键词：
胆汁酸（BA）参与坏死性小肠结肠炎（NEC）的发生，主要发生在早产儿中。我们的目的是确定在早产儿中的BA的变化，并验证其在NEC检测的潜在价值。采用靶向液相色谱-串联质谱法（LC-MS/MS）测定健康早产儿和NEC患者血浆中的BA。通过对健康早产儿血中BAs水平的分析，我们发现血中BAs浓度与性别、胎龄、出生体重、出生方式、出生后喂养方式有关。NEC患者血浆TCA、GCA、TCDCA、GCDCA、原发性BA和总BA水平以及原发性/继发性BA比值降低，而DCA、UDCA和继发性BA水平升高。原发性/继发性BA比值（临界点62.9）可有效区分NEC与健康早产儿，AUC为0.9，灵敏度为94.5%，特异性为78.1%。将该比值与NEC的高危因素相结合，可以更好地区分NEC和对照，AUC为0.95。重要的是，在手术NEC的婴儿中发现原发性/继发性BA比率显著低于非手术NEC病例。以28.7分为界值，鉴别手术NEC和非手术NEC的敏感性和特异性分别为76.9%和100%。因此，我们的研究表明，血浆中的原发性/继发性BA比率可以区分NEC与健康早产儿，并有效区分手术NEC与非手术NEC。因此，LC-MS/MS有望成为一种新的测量平台，用于区分最需要密切监测或早期手术干预的婴儿。
Bile acids (BAs) are involved in the development of necrotizing enterocolitis (NEC), which mainly occurs in preterm infants. We aim to identify the change of BAs in preterm infants and validate its potential value in the detection of NEC. Targeted liquid chromatography–tandem mass spectrometry (LC-MS/MS) was performed to measure the plasma BAs in healthy preterm infants and patients with NEC. By analyzing the level of BAs in healthy preterm infants, we found that the plasma concentrations of BAs were related to sex, gestational/postnatal age, birth weight, mode of birth, and feeding type after birth. The plasma levels of TCA, GCA, TCDCA, GCDCA, primary BAs, and total BAs and the primary/secondary BA ratio were decreased, while DCA, UDCA, and secondary BAs were increased in NEC. The primary/secondary BA ratio (cutoff point 62.9) can effectively differentiate NEC from healthy preterm infants, with an AUC of 0.9, a sensitivity of 94.5%, and a specificity of 78.1%. Combining the ratio with high-risk factors of NEC can better distinguish between NEC and control, with an AUC of 0.95. Importantly, significantly lower levels of primary/secondary BA ratio were found in infants with surgical NEC than in nonsurgical NEC cases. The cutoff point of 28.7 identified surgical NEC from nonsurgical NEC with sensitivity and specificity of 76.9% and 100%. Thus, our study identified that the primary/secondary BA ratio in the plasma can differentiate NEC from healthy preterm infants and effectively differentiate the surgical NEC from nonsurgical NEC. Therefore, LC-MS/MS was expected to be a novel measurement platform used to distinguish infants who are most in need of close monitoring or early surgical intervention.
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通讯作者：
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影响因子：
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