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粪便肠道微生物群和氨基酸作为儿童炎症性肠病的非侵入性诊断生物标志物。

Fecal gut microbiota and amino acids as noninvasive diagnostic biomarkers of Pediatric inflammatory bowel disease.

作者信息

Vermeer Eva, Jagt Jasmijn Z, Lap Eline M, Struys Eduard A, Budding Andries E, Verhoeven-Duif Nanda M, Bosma Marjolein, van Limbergen Johan E, Koot Bart G P, de Jonge Robert, Benninga Marc A, Acharjee Animesh, de Boer Nanne K H, de Meij Tim G J

机构信息

Department of Paediatric Gastroenterology, Emma Children's Hospital, Amsterdam UMC, Amsterdam, The Netherlands.

Amsterdam Gastroenterology Endocrinology Metabolism (AGEM) Research Institute, Amsterdam UMC, Amsterdam, The Netherlands.

出版信息

Gut Microbes. 2025 Dec;17(1):2517828. doi: 10.1080/19490976.2025.2517828. Epub 2025 Jun 12.

Abstract

BACKGROUND AND AIMS

Fecal calprotectin (FCP) has limited specificity as diagnostic biomarker of pediatric inflammatory bowel disease (IBD), leading to unnecessary invasive endoscopies. This study aimed to develop and validate a fecal microbiota and amino acid (AA)-based diagnostic model.

METHODS

Fecal samples from a discovery cohort ( IBD and healthy controls [HC]) were used to develop the diagnostic model. This model was applied in a validation cohort ( IBD and controls with gastrointestinal symptoms [CGI]). Microbiota and AAs were analyzed using interspace profiling and liquid chromatography-mass spectrometry techniques, respectively. Machine learning techniques were used to build the diagnostic model.

RESULTS

In the discovery cohort (58 IBD, 59 hC), two microbial species ( and ) and four AAs (leucine, ornithine, taurine, and alpha-aminoadipic acid [AAD]) combined allowed for discrimination between both subgroups (AUC 0.94, 95% CI [0.89, 0.98]). In the validation cohort (43 IBD, 38 CGI), this panel of six markers could differentiate patients with IBD from CGI with an AUC of 0.84, 95% CI [0.67, 0.95]). Leucine showed the best diagnostic performance (AUC 0.89, 95% CI [0.81, 0.95]).

CONCLUSIONS

Leucine might serve as adjuvant noninvasive biomarker in the diagnostic work-up of pediatric IBD. Future research should investigate whether the combination of leucine with FCP could improve specificity and may help tailor the course of diagnostics.

摘要

背景与目的

粪便钙卫蛋白(FCP)作为小儿炎症性肠病(IBD)的诊断生物标志物,其特异性有限,导致不必要的侵入性内镜检查。本研究旨在开发并验证一种基于粪便微生物群和氨基酸(AA)的诊断模型。

方法

使用来自发现队列(IBD患者和健康对照[HC])的粪便样本开发诊断模型。该模型应用于验证队列(IBD患者和有胃肠道症状的对照[CGI])。分别使用间隔分析和液相色谱 - 质谱技术分析微生物群和氨基酸。使用机器学习技术构建诊断模型。

结果

在发现队列(58例IBD患者,59例HC)中,两种微生物物种( 和 )与四种氨基酸(亮氨酸、鸟氨酸、牛磺酸和α - 氨基己二酸[AAD])相结合,能够区分两个亚组(AUC为0.94,95% CI [0.89, 0.98])。在验证队列(43例IBD患者,38例CGI)中,这一组六个标志物能够将IBD患者与CGI区分开来,AUC为0.84,95% CI [0.67, 0.95])。亮氨酸表现出最佳诊断性能(AUC为0.89,95% CI [0.81, 0.95])。

结论

亮氨酸可能作为小儿IBD诊断检查中的辅助非侵入性生物标志物。未来研究应调查亮氨酸与FCP联合使用是否可提高特异性,并可能有助于调整诊断流程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a018/12164387/d81d410bed4e/KGMI_A_2517828_F0001_OC.jpg

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