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早产儿坏死性小肠结肠炎发生前的纵向粪便微生物群和挥发性代谢组学:一项病例对照研究。

Longitudinal fecal microbiota and volatile metabolomics preceding necrotizing enterocolitis in preterm infants: a case-control study.

作者信息

El Manouni El Hassani S, Frerichs N M, Berkhout D J C, Nijsen T, Knobel H H, Weda H, Xu M, Long X, Wijnoltz L, van Weissenbruch M M, van Kaam A H, Cossey V, Peeters C F W, van Lingen R A, Hulzebos C V, Vijlbrief D C, de Boode W P, Kramer B W, Budding A E, Benninga M A, de Boer N K H, Niemarkt H J, de Meij T G J

机构信息

Department of Pediatric Gastroenterology, Emma Children's Hospital, Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, Amsterdam UMC, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.

Amsterdam Reproduction and Development Research Institute, Amsterdam UMC, Amsterdam, The Netherlands.

出版信息

Sci Rep. 2025 Mar 26;15(1):10419. doi: 10.1038/s41598-025-94692-w.

DOI:10.1038/s41598-025-94692-w
PMID:40140438
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11947453/
Abstract

Alterations in fecal microbiota and volatile organic compound (VOC) profiles of preterm infants have been demonstrated before onset of necrotizing enterocolitis (NEC). However, NEC-specific signatures need to be identified before potential application as predictive biomarker in clinical practice. A prospective multicenter case-control study was conducted to identify preclinical fecal microbiota and VOC profiles of infants that developed NEC. Microbiota analysis (PCR-based IS-pro technique) and VOC analysis (gas chromatography-mass spectrometry) were performed on fecal samples collected up to three days before clinical NEC onset. In 112 infants (56 NEC, 56 matched controls), sufficient number fecal samples were collected for either microbiota or VOC analysis. Prior to NEC onset, Clostridium perfringens (p = 0.023, unadjusted) was more present in infants with NEC, versus controls. VOC analysis showed a clear distinction between fecal profiles of NEC cases and controls (area under the curve = 0.82). Fourteen unique VOC features contributed to this discrimination. Fecal microbiota and VOC profiles may serve as early indicators of NEC, and allow for increased understanding of pathophysiological mechanisms of NEC, but larger validation cohorts are needed before an overarching NEC-specific predictive microbiota-based biomarker can be implemented.

摘要

在坏死性小肠结肠炎(NEC)发作之前,已证实早产儿的粪便微生物群和挥发性有机化合物(VOC)谱存在改变。然而,在作为预测性生物标志物应用于临床实践之前,需要确定NEC特异性特征。开展了一项前瞻性多中心病例对照研究,以确定发生NEC的婴儿的临床前粪便微生物群和VOC谱。在临床NEC发作前三天内收集的粪便样本上进行微生物群分析(基于PCR的IS-pro技术)和VOC分析(气相色谱-质谱法)。在112名婴儿(56例NEC,56例匹配对照)中,收集了足够数量的粪便样本用于微生物群或VOC分析。在NEC发作前,与对照组相比,产气荚膜梭菌在NEC婴儿中更为常见(p = 0.023,未校正)。VOC分析显示NEC病例和对照的粪便谱有明显区别(曲线下面积 = 0.82)。14个独特的VOC特征促成了这种区分。粪便微生物群和VOC谱可能作为NEC的早期指标,并有助于加深对NEC病理生理机制的理解,但在实施基于微生物群的总体NEC特异性预测性生物标志物之前,需要更大的验证队列。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73b3/11947453/452a61e26c69/41598_2025_94692_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73b3/11947453/93d101ffa0a6/41598_2025_94692_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73b3/11947453/0b9295fa1355/41598_2025_94692_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73b3/11947453/54be78a239de/41598_2025_94692_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73b3/11947453/452a61e26c69/41598_2025_94692_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73b3/11947453/93d101ffa0a6/41598_2025_94692_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73b3/11947453/0b9295fa1355/41598_2025_94692_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73b3/11947453/158718fedb78/41598_2025_94692_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73b3/11947453/54be78a239de/41598_2025_94692_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73b3/11947453/452a61e26c69/41598_2025_94692_Fig5_HTML.jpg

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本文引用的文献

1
The Potential of Fecal Volatile Organic Compound Analysis for the Early Diagnosis of Late-Onset Sepsis in Preterm Infants: A Narrative Review.粪便挥发性有机化合物分析在早产儿晚发性败血症早期诊断中的潜力:一项叙述性综述。
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Abnormalities in microbial composition and function in infants with necrotizing enterocolitis: A single-center observational study.
坏死性小肠结肠炎婴儿的微生物组成和功能异常:一项单中心观察性研究。
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Nutrients. 2022 Sep 18;14(18):3859. doi: 10.3390/nu14183859.
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Gut microbiota and short-chain fatty acids may be new biomarkers for predicting neonatal necrotizing enterocolitis: A pilot study.肠道微生物群和短链脂肪酸可能是预测新生儿坏死性小肠结肠炎的新生物标志物:一项初步研究。
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