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一项使用基质辅助激光解吸电离质谱成像的非靶向代谢组学研究揭示了与肠道炎症相关的区域特异性生物标志物。

An untargeted metabolomic study using MALDI-mass spectrometry imaging reveals region-specific biomarkers associated with bowel inflammation.

作者信息

Ponzoni Adele, Speca Silvia, Hartle Matthew, Gerstenberg Amandine, Tomezyk Aurore, Senechal Victor, Karnik Shane, Dubuquoy Laurent, Launay David, Deprez-Poulain Rebecca, Gaudin Mathieu, Ramos Corinne, Deprez Benoit

机构信息

Aliri France SAS, Parc Eurasanté, 59120, Loos, France.

U1286-INFINITE-Institute for Translational Research in Inflammation, CHU Lille, Inserm, Univ. Lille, 59000, Lille, France.

出版信息

Metabolomics. 2024 Dec 14;21(1):5. doi: 10.1007/s11306-024-02200-4.

DOI:10.1007/s11306-024-02200-4
PMID:39674857
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11646223/
Abstract

INTRODUCTION

Inflammatory bowel diseases (IBDs) are chronic immune driven intestinal disorders with marked metabolic alteration. Mass spectrometry imaging (MSI) enables the direct visualization of biomolecules within tissues and facilitates the study of metabolic changes. Integrating multiple spatial information sources is a promising approach for discovering new biomarkers and understanding biochemical alteration within the context of the disease.

OBJECTIVE

This study evaluates the metabolomic changes in gut tissue samples from a preclinical model of spontaneous colitis, the HLA-B27/hβ2m transgenic rat, to uncover disease biomarkers.

METHODS

We applied MSI to study the biochemical profile of bowel samples from HLA-B27/hβ2m transgenic and WT control rats in an unbiased manner. Statistical comparison was used to identify discriminative features. Some features were annotated using LC-MS/MS. The significance of these discriminative features was evaluated based on their distribution within histological layers and the presence of immune infiltration.

RESULTS

We identified spatially resolved changes in the metabolomic pattern of HLA-B27 samples compared to WT controls. Out of the 275 discriminative features identified, 83 were annotated as metabolites. Two functional groups of discriminative metabolites were discussed as markers of gut barrier impairment and immune cell infiltration.

CONCLUSION

MS imaging's spatial dimension provides insights into disease mechanisms through the identification of spatially resolved biomarkers.

摘要

引言

炎症性肠病(IBD)是由慢性免疫驱动的肠道疾病,伴有明显的代谢改变。质谱成像(MSI)能够直接可视化组织内的生物分子,并有助于研究代谢变化。整合多个空间信息源是发现新生物标志物和理解疾病背景下生化改变的一种有前景的方法。

目的

本研究评估来自自发性结肠炎临床前模型HLA-B27/hβ2m转基因大鼠的肠道组织样本中的代谢组学变化,以发现疾病生物标志物。

方法

我们应用MSI以无偏倚的方式研究HLA-B27/hβ2m转基因大鼠和野生型对照大鼠肠道样本的生化特征。使用统计比较来识别有鉴别力的特征。一些特征通过液相色谱-串联质谱(LC-MS/MS)进行注释。基于这些有鉴别力的特征在组织学层面的分布以及免疫浸润的存在来评估其意义。

结果

与野生型对照相比,我们在HLA-B27样本的代谢组学模式中确定了空间分辨的变化。在鉴定出的275个有鉴别力的特征中,83个被注释为代谢物。讨论了两组有鉴别力的代谢物功能类别作为肠道屏障损伤和免疫细胞浸润的标志物。

结论

MS成像的空间维度通过识别空间分辨的生物标志物为疾病机制提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f96/11646223/9a617a424735/11306_2024_2200_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f96/11646223/e7c6047a02d0/11306_2024_2200_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f96/11646223/2dbb67f6fb6b/11306_2024_2200_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f96/11646223/a0a2cbe306a9/11306_2024_2200_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f96/11646223/6b195efc86b8/11306_2024_2200_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f96/11646223/9a617a424735/11306_2024_2200_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f96/11646223/e7c6047a02d0/11306_2024_2200_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f96/11646223/2dbb67f6fb6b/11306_2024_2200_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f96/11646223/a0a2cbe306a9/11306_2024_2200_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f96/11646223/6b195efc86b8/11306_2024_2200_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f96/11646223/9a617a424735/11306_2024_2200_Fig5_HTML.jpg

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