Clinical features of the study participants

Chronic alcohol intake alters the plasma metabolome compared to healthy controls.

a Principal component analysis score plot of the plasma metabolomic features between healthy controls and persons with AUD at T1. QC samples are colored in orange. b Top 50 annotated metabolites ranked on their variable importance in projections (VIP) scores in the sPLS-DA model. c Volcano plot depicting the effect size (Cohen’s D) and −Log10 transformed q values derived from Welch’s t-test analysis of the metabolomic features different between healthy controls and persons with AUD at T1. d Annotated metabolites having significant association (Spearman p<0.05) with alcohol intake (g/day) in persons with AUD at T1. Circle size refers to the level of significance, blue gradient color to the strength of negative while red to the strength of positive correlation coefficients. 3-CMPFP 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid; AC acylcarnitine; CLA conjugated linoleic acid; FA fatty acid; LPC lysophosphatidylcholine; LPE lysophosphatidylethanolamine; PC phosphatidylcholine; PE phosphatidylethanolamine; SM sphingomyelin.

3-week alcohol withdrawal shapes the plasma metabolome.

a Scores plot of the sparse partial least square discriminant analysis (sPLS-DA) of the plasma metabolomes at the start (T1) and end (T2) of the alcohol withdrawal in persons with AUD. b Top 50 annotated metabolites having a variable importance in projection (VIP) score of > 1.5 in the sPLS-DA model. c Lollipop plot of the effect size (Cohen’s D) and −Log10 transformed q values of the altered annotated metabolites between AUD T1 and healthy controls as well as AUD T1 and AUD T2. Circle size refers to the level of significance, grey color to the comparison between controls and AUD T1, orange color to relative increase while violet to relative decrease towards the end of alcohol withdrawal (T2). AC acylcarnitine; FA fatty acid; LPC lysophosphatidylcholine; LPE lysophosphatidylethanolamine; PC phosphatidylcholine.

Plasma metabolites associated with psychological symptom scores.

Heatmap of the annotated metabolites having significant (p<0.05) Spearman correlation with one or more psychological symptom score of obsession, compulsion, alcohol craving, anxiety state or depression. Circle size refers to the level of significance, blue gradient color to the strength of negative while red to the strength of positive correlation coefficients. AC acylcarnitine; FA fatty acid; GM gut microbiota; LPC lysophosphatidylcholine; LPE lysophosphatidylethanolamine; PC phosphatidylcholine.

Overlapping metabolites within the plasma and brain metabolome.

a Venn diagram of the annotated plasma metabolites that are also present in the frontal cortex and cerebrospinal fluid metabolome. b Significantly altered (p<0.05) frontal cortex metabolites with a corresponding plasma metabolite showing an association with one or more psychological symptom score. c Significantly altered (p<0.05) cerebrospinal fluid metabolite with a corresponding plasma metabolite showing an association with one or more psychological symptom score. Data expressed as mean ± SD with individual values shown. Statistical values derived from Welch’s t-test comparing metabolomic features between control and alcohol groups.