Changes in the Human Metabolome Associated With Alcohol Use: A Review

Abstract

Aims: The metabolome refers to the functional status of the cell, organ, or the whole body. Metabolomic methods measure the metabolome (metabolite profile) which can be used to examine disease progression and treatment responses. Here, our aim was to review metabolomics studies examining effects of alcohol use in humans. Methods: We performed a literature search using PubMed and Web of Science for reports on changes in the human metabolite profile associated with alcohol use; we found a total of 23 articles published before end of 2018. Results: Most studies had investigated plasma, serum or urine samples; only four studies had examined other sample types (liver, faeces, and broncho-alveolar lavage fluid). Levels of 51 metabolites were altered in two or more of the reviewed studies. Alcohol use was associated with changes in the levels of lipids and amino acids. In general, levels of fatty acids, phosphatidylcholine diacyls and steroid metabolites tended to increase, whereas those of phosphatidylcholine acyl-alkyls and hydroxysphingomyelins declined. Common alterations in circulatory levels of amino acids included decreased levels of glutamine, and increased levels of tyrosine and alanine. Conclusions: More studies, especially with a longitudinal study design, or using more varied sample materials (e.g. organs or saliva), are needed to clarify alcohol-induced diseases and alterations at a target organ level. Hopefully, this will lead to the discovery of new treatments, improved recognition of individuals at high risk and the identification of those subjects who would benefit most from certain treatments.

Changes in Circulating Metabolome Precede Alcohol‐Related Diseases in Middle‐Aged Men: A Prospective Population‐Based Study With a 30‐Year Follow‐Up

“…In the present study, high self-reported alcohol use was associated with alterations in different amino acids, glycerophospholipids, steroid hormones, pyrimidines, and fatty acids (Table 2). These results are in line with previous studies showing that alcohol use alters the circulating metabolome in these compound classes (Heikkinen et al, 2019;Jaremek et al, 2013;Lacruz et al, 2016;Lehikoinen et al, 2018;Pallister et al, 2016;van Roekel et al, 2018;Voutilainen and K€ arkk€ ainen, 2019;W€ urtz et al, 2016;Zheng et al, 2014); it is also known that the levels of compounds in these classes are altered in organs like brain and liver in association with alcohol use disorder (K€ arkk€ ainen et al, 2016;Kashem et al, 2016;Schofield et al, 2017). Moreover, alterations in metabolites associated with gut microbiota, like 3-indolepropionic acid and hippuric acid, were evident between the study groups.…”

“…For example, high glutamate levels at the baseline seem to predict favorable responses to acamprosate treatment (Hinton et al, 2017;Nam et al, 2015). However, most of the studies so far have been cross-sectional or case-control studies, where persons with heavy alcohol use history are compared to light drinking controls, where it is impossible to say which of the changes in the metabolome precede the diagnosis of alcoholrelated disease (Voutilainen and K€ arkk€ ainen, 2019).…”

“…The circulating metabolome, measured from serum or plasma samples, could offer a novel opportunity to identify those individuals who are at risk of developing alcohol‐related diseases in the future, since alcohol use has been associated with alterations in the circulating metabolome in humans (for a review, see Voutilainen and Kärkkäinen, 2019). For example, heavy alcohol use has been associated with higher levels of glutamate, tyrosine, phosphatidylcholine diacyls, and fatty acids like palmitoleate (FA 16:1), as well as with lower levels of glutamine, serotonin, and phosphatidylcholine acyl‐alkyls when compared to low drinking subjects (Harada et al, 2016; Jaremek et al, 2013; Lacruz et al, 2016; Lehikoinen et al, 2018; Pallister et al, 2016; van Roekel et al, 2018; Würtz et al, 2016; Zheng et al, 2014).…”

A Pilot Metabolomic Study on Myocardial Injury Caused by Chronic Alcohol Consumption—Alcoholic Cardiomyopathy

“…In view of the morbidity and mortality of ACM, many studies have explored the pathogenesis of ACM in recent years. Although previous studies have reported metabolomics profiles after alcohol consumption, most studies have chosen serum or plasma as the research object [7]. However, systematic factors in a living organism may affect blood circulation, and the observed metabolic changes in circulating serum or plasma may not only be due to the myocardial injury induced by chronic alcohol consumption [8,9].…”

Hair Metabolomics in Animal Studies and Clinical Settings

“…The metabolome can be divided into three categories: All endogenous metabolites in living organisms, microbial metabolites produced by microorganisms, and all foreign metabolites derived from xenobiotics [1]. Metabolomics, a holistic analytical approach to studying metabolomes, is a powerful tool in understanding the comprehensive changes in metabolic responses in living systems induced by external stimuli or genetic alterations and is the endpoint of the omics cascade [2,3,4,5]. Unlike genomics, transcriptomics, and proteomics, metabolomics reflects the phenotype of living things, enabling us to observe simultaneous changes in many metabolites, thus aiding the discovery of biomarkers for disease diagnosis and facilitating the determination of the metabolic effects on toxicity and the exploration of the action mechanisms in pathogenesis [6,7,8,9,10,11,12,13].…”