
Chronic alcohol abuse and short-term abstinence alter the blood metabolome, with changes in lipids, microbial metabolites, and caffeine derivatives correlating with psychological symptoms like anxiety, depression, and alcohol craving in patients with alcohol use disorder.


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Alcohol use disorder (AUD) is a global health problem with limited therapeutic options. The biochemical mechanisms that lead to alcohol addiction 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. In this study, we investigated the impact of chronic alcohol abuse, and of a three-week period of alcohol abstinence, on the blood metabolome (non-targeted LC-MS metabolomics analysis) in 96 patients diagnosed with severe alcohol use disorder (AUD). 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 AUD 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 abuse 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 post-mortem 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. Our data allow to for the identification of neuroactive metabolites, from interactions between food components and microbiota, which may represent new targets in the management of neuropsychiatric diseases such as AUD.

The study was registered at [clinicaltrial.gov][1] under the identification number [NCT03803709][2].

### Competing Interest Statement

OK and KH are founders of Afekta Technologies Ltd. The other authors report no financial interests or potential conflicts of interest.

 [1]: http://clinicaltrial.gov
 [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT03803709&atom=%2Fbiorxiv%2Fearly%2F2024%2F02%2F29%2F2024.02.27.582239.atom

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

metabolomic-profiling-reveals-new-neuroactive-targets-for-managing-psychological-symptoms-in-alcohol-use-disorder


Metabolomic Profiling Reveals New Neuroactive Targets for Managing Psychological Symptoms in Alcohol Use Disorder
