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接受奥瑞珠单抗治疗的多发性硬化症患者的色氨酸途径分析

Tryptophan pathway profiling in multiple sclerosis patients treated with ocrelizumab.

作者信息

Ricci Carolina, Pivetta Matteo, Martinis Eleonora, Valeri Viviana, Colliva Carolina, Giacchè Nicola, Lorenzut Simone, Cargnelutti Daniela, Frossi Barbara, Tonon Silvia

机构信息

Department of Medicine, University of Udine, Udine, Italy.

Tes Pharma S.r.l., Corciano, Italy.

出版信息

Front Immunol. 2025 Jun 9;16:1603663. doi: 10.3389/fimmu.2025.1603663. eCollection 2025.

Abstract

INTRODUCTION

L-Tryptophan (Trp) metabolism is impaired across various chronic inflammatory pathologies, including Multiple Sclerosis (MS). Trp processing relies on three metabolic routes, namely Kynurenine, Serotonin and Indole pathways. The host microbiota significantly impacts Trp metabolism, primarily by being responsible for Indole metabolites production and secondarily by shaping both Kynurenine and Serotonin pathways. Pathological conditions and pharmaceutical treatments can elicit changes in microbial populations, leading to alterations in metabolites production and therefore determining rearrangements in host metabolism. Currently, no simultaneous exploration and comparison of all three Trp related metabolic routes has been performed in the context of MS patients before and after Ocrelizumab (OCR) treatment.

METHODS

By performing mass spectrometry on plasma samples collected from healthy controls and MS patients before and six months after OCR treatment we provided a comparative investigation of Trp metabolomics profile.

RESULTS AND DISCUSSION

Our data points out to concurrent alterations of Trp-related pathways among both OCR treated and untreated MS patients. Furthermore, MS treated patients presented a pattern resembling health state for various metabolites across the pathways. The results reported in our research may contribute to unveiling new perspectives and understanding regarding MS pathogenetic mechanisms.

摘要

引言

在包括多发性硬化症(MS)在内的各种慢性炎症性疾病中,L-色氨酸(Trp)代谢均受到损害。色氨酸的代谢依赖于三条代谢途径,即犬尿氨酸、5-羟色胺和吲哚途径。宿主微生物群对色氨酸代谢有显著影响,主要负责吲哚代谢产物的产生,其次通过塑造犬尿氨酸和5-羟色胺途径来发挥作用。病理状况和药物治疗可引起微生物种群的变化,导致代谢产物产生的改变,从而决定宿主代谢的重新排列。目前,在奥瑞珠单抗(OCR)治疗前后的MS患者中,尚未对所有三条与色氨酸相关的代谢途径进行同时探索和比较。

方法

通过对从健康对照者以及OCR治疗前和治疗后六个月的MS患者采集的血浆样本进行质谱分析,我们对色氨酸代谢组学谱进行了比较研究。

结果与讨论

我们的数据指出,在接受OCR治疗和未接受治疗的MS患者中,与色氨酸相关的途径同时发生了改变。此外,接受治疗的MS患者在各途径中的多种代谢产物呈现出类似健康状态的模式。我们研究中报告的结果可能有助于揭示有关MS发病机制的新观点和理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18b9/12183176/9a67c917ad93/fimmu-16-1603663-g001.jpg

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