补充菊粉对酒精使用障碍患者粪便和血液代谢组的影响：一项随机对照饮食干预研究。

Effect of inulin supplementation on fecal and blood metabolome in alcohol use disorder patients: A randomised, controlled dietary intervention.

作者信息

Amadieu Camille, Ahmed Hany, Leclercq Sophie, Koistinen Ville, Leyrolle Quentin, Stärkel Peter, Bindels Laure B, Layé Sophie, Neyrinck Audrey M, Kärkkäinen Olli, De Timary Philippe, Hanhineva Kati, Delzenne Nathalie M

机构信息

Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, Brussels, Belgium; Université de Bordeaux, INRAE, Bordeaux INP, NutriNeurO, UMR 1286, F-33000 Bordeaux, France.

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

出版信息

Clin Nutr ESPEN. 2025 Apr;66:361-371. doi: 10.1016/j.clnesp.2025.01.046. Epub 2025 Jan 27.

DOI:10.1016/j.clnesp.2025.01.046

PMID:39864520

Abstract

BACKGROUND AND AIMS

Alcohol Use Disorder (AUD) is a psychiatric disorder characterized notably by gut microbial dysbiosis and insufficient dietary fiber (DF) intake. This study aims to investigate the effect of DF placebo-controlled intervention in patients suffering from AUD during a three-week period of alcohol withdrawal, in order to discover microbial-derived metabolites that could be involved in metabolic and behavioral status.

METHODS

A randomized, double-blind, placebo-controlled study was performed with 50 AUD patients supplemented with inulin (prebiotic DF) or maltodextrin (placebo) during 17 days. Fecal microbiota composition, plasma and fecal metabolomics (liquid chromatography coupled to mass spectrometry), blood markers of inflammation and hepatic alterations, and psychological assessment (questionnaires) were analyzed before and after the intervention.

RESULTS

Fecal metabolomics revealed 14 metabolites significantly modified by inulin versus placebo treatment (increased N8-acetylspermidine and decreased indole-3-butyric acid, 5-amino valeric acid betaine (5-AVAB) and bile acids). Thirteen plasma metabolites differentiated both treatments (higher levels of long-chain fatty acids, medium-chain acylcarnitines and sphingomyelin species, and reduced 3-methylhistidine by inulin versus placebo). Fecal Lachnoclostridium correlated with 6 of the identified fecal metabolites, whereas plasma lipidic moieties positively correlated with fecal Ruminococcus torques group and Flavonifractor. Interestingly, parameters reflecting liver alterations inversely correlated with sphingomyelin (SM 36:2).

CONCLUSIONS

Three weeks of inulin supplementation during alcohol withdrawal leads to specific and different changes in the plasma and fecal metabolome of AUD patients, some of these gut microbiota-related metabolites being correlated with liver function.

TRIAL REGISTRATION

NCT03803709, https://clinicaltrials.gov/ct2/show/NCT03803709.

摘要

背景与目的

酒精使用障碍（AUD）是一种精神障碍，其显著特征为肠道微生物群失调和膳食纤维（DF）摄入不足。本研究旨在调查在为期三周的酒精戒断期内，DF安慰剂对照干预对AUD患者的影响，以发现可能与代谢和行为状态有关的微生物衍生代谢产物。

方法

对50例AUD患者进行了一项随机、双盲、安慰剂对照研究，在17天内为患者补充菊粉（益生元DF）或麦芽糊精（安慰剂）。在干预前后分析粪便微生物群组成、血浆和粪便代谢组学（液相色谱-质谱联用）、炎症和肝脏改变的血液标志物以及心理评估（问卷调查）。

结果

粪便代谢组学显示，与安慰剂治疗相比，菊粉治疗使14种代谢产物发生显著改变（N8-乙酰亚精胺增加，吲哚-3-丁酸、5-氨基戊酸甜菜碱（5-AVAB）和胆汁酸减少）。13种血浆代谢产物区分了两种治疗方法（与安慰剂相比，菊粉使长链脂肪酸、中链酰基肉碱和鞘磷脂水平升高，3-甲基组氨酸降低）。粪便中的迟缓梭菌与6种已鉴定的粪便代谢产物相关，而血浆脂质部分与粪便扭链瘤胃球菌群和黄酮分解菌呈正相关。有趣的是，反映肝脏改变的参数与鞘磷脂（SM 36:2）呈负相关。