Serum Metabolites Relate to Mucosal and Transmural Inflammation in Paediatric Crohn Disease.

Ricardo G Suarez, Namitha Guruprasad, Ganesh Tata, Zhengxiao Zhang, Gili Focht, Daniel McClement, Víctor Manuel Navas-López, Sibylle Koletzko, Anne M Griffiths, Oren Ledder, Lissy de Ridder, David Wishart, Ben Nichols, Konstantinos Gerasimidis, Dan Turner, Eytan Wine
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Abstract

Background and aims: We aimed to identify serum metabolites associated with mucosal and transmural inflammation in paediatric Crohn disease [pCD].

Methods: In all, 56 pCD patients were included through a pre-planned sub-study of the multicentre, prospective, ImageKids cohort, designed to develop the Paediatric Inflammatory Crohn magnetic resonance enterography [MRE] Index [PICMI]. Children were included throughout their disease course when undergoing ileocolonoscopy and MRE and were followed for 18 months, when MRE was repeated. Serum metabolites were identified using liquid chromatography/mass spectroscopy. Outcomes included: PICMI, the simple endoscopic score [SES], faecal calprotectin [FCP], and C-reactive protein [CRP], to assess transmural, mucosal, and systemic inflammation, respectively. Random forest models were built by outcome. Maximum relevance minimum redundancy [mRMR] feature selection with a j-fold cross-validation scheme identified the best subset of features and hyperparameter settings.

Results: Tryptophan and glutarylcarnitine were the top common mRMR metabolites linked to pCD inflammation. Random forest models established that amino acids and amines were among the most influential metabolites for predicting transmural and mucosal inflammation. Predictive models performed well, each with an area under the curve [AUC] > 70%. In addition, serum metabolites linked with pCD inflammation mainly related to perturbations in the citrate cycle [TCA cycle], aminoacyl-tRNA biosynthesis, tryptophan metabolism, butanoate metabolism, and tyrosine metabolism.

Conclusions: We extend on recent studies, observing differences in serum metabolites between healthy controls and Crohn disease patients, and suggest various associations of serum metabolites with transmural and mucosal inflammation. These metabolites could improve the understanding of pCD pathogenesis and assessment of disease severity.

血清代谢物与小儿克罗恩病的黏膜和跨膜炎症有关
背景与目的我们旨在确定与小儿克罗恩病(pCD)粘膜和跨膜炎症相关的血清代谢物:多中心、前瞻性、ImageKids队列的一项预先计划的子研究纳入了56名小儿克罗恩病患者,该研究旨在开发小儿炎症性克罗恩病MRE指数(PICMI)。儿童在接受回肠结肠镜检查和磁共振肠造影术(MRE)的整个病程中都被纳入研究范围,并在重复接受 MRE 检查时接受 18 个月的随访。使用液相色谱/质谱法鉴定血清代谢物。结果包括PICMI、简单内镜评分 (SES)、粪便钙蛋白 (FCP) 和 C 反应蛋白 (CRP),分别用于评估跨壁、粘膜和全身炎症。按结果建立随机森林模型。最大相关性最小冗余(mRMR)特征选择与j-fold交叉验证方案确定了最佳特征子集和超参数设置:结果:色氨酸和戊二酰肉碱是与 pCD 炎症相关的最常见的 mRMR 代谢物。随机森林模型表明,氨基酸和胺是预测跨壁和粘膜炎症最有影响力的代谢物。预测模型表现良好,每个模型的曲线下面积(AUC)均大于 70%。此外,与 pCD 炎症有关的血清代谢物主要与柠檬酸循环(TCA 循环)、氨基酰-tRNA 生物合成、色氨酸代谢、丁酸代谢和酪氨酸代谢的紊乱有关:我们扩展了近期的研究,观察到健康对照组和克罗恩病患者血清代谢物的差异,并提出了血清代谢物与跨膜和粘膜炎症的各种关联。这些代谢物可增进对克罗恩病发病机制的了解并评估疾病的严重程度。
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