血液代谢组学分析揭示了严重酒精使用障碍相关心理症状治疗的新靶点。

Blood metabolomic profiling reveals new targets in the management of psychological symptoms associated with severe alcohol use disorder.

机构信息

Laboratory of Nutritional Psychiatry, Institute of Neuroscience, UCLouvain, Université catholique de Louvain, Brussels, Belgium.

Food Sciences Unit, Department of Life Technologies, University of Turku, Turku, Finland.

出版信息

Elife. 2024 Nov 29;13:RP96937. doi: 10.7554/eLife.96937.

DOI:10.7554/eLife.96937

PMID:39611656

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11606602/

Abstract

BACKGROUND

Alcohol use disorder (AUD) is a global health problem with limited therapeutic options. The biochemical mechanisms that lead to this disorder are not yet fully understood, and in this respect, metabolomics represents a promising approach to decipher metabolic events related to AUD. The plasma metabolome contains a plethora of bioactive molecules that reflects the functional changes in host metabolism but also the impact of the gut microbiome and nutritional habits.

METHODS

In this study, we investigated the impact of severe AUD (sAUD), and of a 3-week period of alcohol abstinence, on the blood metabolome (non-targeted LC-MS metabolomics analysis) in 96 sAUD patients hospitalized for alcohol withdrawal.

RESULTS

We found that the plasma levels of different lipids ((lyso)phosphatidylcholines, long-chain fatty acids), short-chain fatty acids (i.e. 3-hydroxyvaleric acid) and bile acids were altered in sAUD patients. In addition, several microbial metabolites, including indole-3-propionic acid, p-cresol sulfate, hippuric acid, pyrocatechol sulfate, and metabolites belonging to xanthine class (paraxanthine, theobromine and theophylline) were sensitive to alcohol exposure and alcohol withdrawal. 3-Hydroxyvaleric acid, caffeine metabolites (theobromine, paraxanthine, and theophylline) and microbial metabolites (hippuric acid and pyrocatechol sulfate) were correlated with anxiety, depression and alcohol craving. Metabolomics analysis in postmortem samples of frontal cortex and cerebrospinal fluid of those consuming a high level of alcohol revealed that those metabolites can be found also in brain tissue.

CONCLUSIONS

Our data allow the identification of neuroactive metabolites, from interactions between food components and microbiota, which may represent new targets arising in the management of neuropsychiatric diseases such as sAUD.

FUNDING

Gut2Behave project was initiated from ERA-NET NEURON network (Joint Transnational Call 2019) and was financed by Academy of Finland, French National Research Agency (ANR-19-NEUR-0003-03) and the Fonds de la Recherche Scientifique (FRS-FNRS; PINT-MULTI R.8013.19, Belgium). Metabolomics analysis of the TSDS samples was supported by grant from the Finnish Foundation for Alcohol Studies.

摘要

背景

酒精使用障碍（AUD）是一种全球性的健康问题，治疗选择有限。导致这种疾病的生化机制尚未完全了解，在这方面，代谢组学代表了一种破译与 AUD 相关的代谢事件的有前途的方法。血浆代谢组包含大量生物活性分子，反映了宿主代谢的功能变化，也反映了肠道微生物组和营养习惯的影响。

方法

在这项研究中，我们研究了严重 AUD（sAUD）以及为期 3 周的戒酒期对 96 名因酒精戒断而住院的 sAUD 患者血液代谢组（非靶向 LC-MS 代谢组学分析）的影响。

结果

我们发现 sAUD 患者的不同脂质（溶血磷脂酰胆碱、长链脂肪酸）、短链脂肪酸（即 3-羟基丁酸）和胆汁酸的血浆水平发生了改变。此外，几种微生物代谢物，包括吲哚-3-丙酸、对甲酚硫酸盐、马尿酸、儿茶酚硫酸盐和黄嘌呤类代谢物（副黄嘌呤、可可碱和茶碱），对酒精暴露和酒精戒断敏感。3-羟基丁酸、咖啡因代谢物（可可碱、副黄嘌呤和茶碱）和微生物代谢物（马尿酸和儿茶酚硫酸盐）与焦虑、抑郁和酒精渴求有关。对摄入高酒精量的额皮质和脑脊液的死后样本进行代谢组学分析表明，这些代谢物也存在于脑组织中。

结论

我们的数据允许识别神经活性代谢物，这些代谢物来自食物成分和微生物群之间的相互作用，它们可能代表管理 AUD 等神经精神疾病时出现的新靶点。

资助

Gut2Behave 项目由 ERA-NET NEURON 网络（2019 年联合跨国呼吁）发起，由芬兰科学院、法国国家研究署（ANR-19-NEUR-0003-03）和比利时佛兰芒研究基金会（FRS-FNRS；PINT-MULTI R.8013.19）共同资助。TSDS 样本的代谢组学分析得到了芬兰酒精研究基金会的资助。