Camille Amadieu , Hany Ahmed , Sophie Leclercq , Ville Koistinen , Quentin Leyrolle , Peter Stärkel , Laure B. Bindels , Sophie Layé , Audrey M. Neyrinck , Olli Kärkkäinen , Philippe De Timary , Kati Hanhineva , Nathalie M. Delzenne
{"title":"Effect of inulin supplementation on fecal and blood metabolome in alcohol use disorder patients: A randomised, controlled dietary intervention","authors":"Camille Amadieu , Hany Ahmed , Sophie Leclercq , Ville Koistinen , Quentin Leyrolle , Peter Stärkel , Laure B. Bindels , Sophie Layé , Audrey M. Neyrinck , Olli Kärkkäinen , Philippe De Timary , Kati Hanhineva , Nathalie M. Delzenne","doi":"10.1016/j.clnesp.2025.01.046","DOIUrl":null,"url":null,"abstract":"<div><h3>Background and aims</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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 <em>Lachnoclostridium</em> correlated with 6 of the identified fecal metabolites, whereas plasma lipidic moieties positively correlated with fecal <em>Ruminococcus torques</em> group and <em>Flavonifractor</em>. Interestingly, parameters reflecting liver alterations inversely correlated with sphingomyelin (SM 36:2).</div></div><div><h3>Conclusions</h3><div>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.</div></div><div><h3>Trial registration</h3><div>NCT03803709, <span><span>https://clinicaltrials.gov/ct2/show/NCT03803709</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":10352,"journal":{"name":"Clinical nutrition ESPEN","volume":"66 ","pages":"Pages 361-371"},"PeriodicalIF":2.6000,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical nutrition ESPEN","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2405457725000476","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"NUTRITION & DIETETICS","Score":null,"Total":0}
引用次数: 0
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.
期刊介绍：
Clinical Nutrition ESPEN is an electronic-only journal and is an official publication of the European Society for Clinical Nutrition and Metabolism (ESPEN). Nutrition and nutritional care have gained wide clinical and scientific interest during the past decades. The increasing knowledge of metabolic disturbances and nutritional assessment in chronic and acute diseases has stimulated rapid advances in design, development and clinical application of nutritional support. The aims of ESPEN are to encourage the rapid diffusion of knowledge and its application in the field of clinical nutrition and metabolism. Published bimonthly, Clinical Nutrition ESPEN focuses on publishing articles on the relationship between nutrition and disease in the setting of basic science and clinical practice. Clinical Nutrition ESPEN is available to all members of ESPEN and to all subscribers of Clinical Nutrition.
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