逆メタボロミクス:炎症性腸疾患のバイオマーカーを発見する新手法(Reverse Metabolomics: New Method Finds Biomarker for Inflammatory Bowel Disease)

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2023-12-05 カリフォルニア大学サンディエゴ校(UCSD)

UC San Diego scientists used “reverse metabolomics” to better understand inflammatory bowel disease on a molecular level. Photo credit: Julien Tromeur/Unsplash

◆最新の研究によれば、微生物叢研究は微生物そのものからその分子への焦点を移しており、新しい手法「逆メタボロミクス」が登場しています。この手法は、有機合成、データサイエンス、質量分析を組み合わせ、微生物叢が分泌する分子と人間の健康への影響を理解するのに役立ちます。
◆初の逆メタボロミクス応用では、数百もの新しい分子が発見され、これが炎症性腸疾患(IBD)の新たな代謝シグネチャを明らかにしました。これらの分子は将来的にIBDのバイオマーカーや治療標的として活用される可能性があります。研究者は、逆メタボロミクスが分子レベルで人体の機能を理解する手助けになるだけでなく、IBDの治療法の創出にも寄与する可能性があると述べています。

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ヒトから化学構造を発見する逆メタボロミクス Reverse metabolomics for the discovery of chemical structures from humans

Emily C. Gentry,Stephanie L. Collins,Morgan Panitchpakdi,Pedro Belda-Ferre,Allison K. Stewart,Marvic Carrillo Terrazas,Hsueh-han Lu,Simone Zuffa,Tingting Yan,Julian Avila-Pacheco,Damian R. Plichta,Allegra T. Aron,Mingxun Wang,Alan K. Jarmusch,Fuhua Hao,Mashette Syrkin-Nikolau,Hera Vlamakis,Ashwin N. Ananthakrishnan,Brigid Boland,Amy Hemperly,Niels Vande Casteele,Frank J. Gonzalez,Clary B. Clish,Ramnik J. Xavier,Hiutung Chu,Erin S. Baker,Andrew D. Patterson,Rob Knight,Dionicio Siegel & Pieter C. Dorrestein
Nature  Published:05 December 2023
DOI:https://doi.org/10.1038/s41586-023-06906-8

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Abstract

Determining structure and phenotypic context of molecules detected in untargeted metabolomics experiments remains challenging. Here, we present reverse metabolomics as a discovery strategy, where MS/MS spectra are acquired from newly synthesized compounds and searched for in public metabolomics data to uncover phenotypic associations. To demonstrate the concept, we broadly synthesized and explored multiple classes of metabolites in humans – N-acyl amides, fatty acid esters of hydroxy fatty acids, bile acid esters and conjugated bile acids. Using repository scale analysis,15,16 we discovered that some conjugated bile acids were associated with inflammatory bowel disease (IBD). Using four distinct human IBD cohorts for validation, we found that Glu, Ile/Leu, Phe, Thr, Trp and Tyr conjugated cholic acids were elevated in Crohn’s disease. Several of these compounds and related structures were shown to affect pathways associated with inflammatory bowel disease, such as interferon-gamma production in CD4+ T cells40 and PXR agonism.41 Bacteria belonging to the Bifidobacterium, Clostridium, and Enterococcus genera were able to produce these bile amidates when cultured. Because searching repositories with MS/MS spectra has only recently become possible, reverse metabolomics approach can now be employed as a general strategy to discover other molecules from human and animal ecosystems.

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