
만성 알코올 섭취와 단기 금주가 혈액 대사체 프로파일에 미치는 영향을 분석하고, 이러한 대사체가 불안, 우울, 알코올 갈망과 같은 심리적 증상과 관련되어 있음을 확인하였다. 이를 통해 새로운 신경활성 대사체를 발견하여 알코올 사용 장애의 관리를 위한 잠재적 타깃으로 제안하였다.


coremsg

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

만성-알코올-섭취가-혈액-대사체에-미치는-영향과-알코올-금단-기간-동안의-변화


만성 알코올 섭취가 혈액 대사체에 미치는 영향과 알코올 금단 기간 동안의 변화
