Alcohol use-associated alterations in the circulating metabolite profile in the general population and in individuals with major depressive disorder

Kärkkäinen, Olli; Tolmunen, Tommi; Kivimäki, Petri; Kurkinen, Karoliina; Ali-Sisto, Toni; Mäntyselkä, Pekka; Valkonen-Korhonen, Minna; Koivumaa-Honkanen, Heli; Honkalampi, Kirsi; Ruusunen, Anu; Velagapudi, Vidya; Lehto, Soili M.

doi:10.1016/j.alcohol.2024.01.005

“…The plasma concentration of hippuric acid has been shown to be 17-fold higher in conventional mice compared with their germ-free counterparts suggesting a substantial contribution of the gut microbiota in its production (46). We showed that blood hippurate levels, that correlated negatively with anxiety, depression and craving, were decreased in AUD patients, as shown in ethanol-treated mice (6) and humans characterized by high alcohol intake and those with major depression (47,48). Urinary hippurate excretion is also decreased in depression, schizophrenia and autism spectrum disorders patients (44).…”

Section: Discussionmentioning

confidence: 80%

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

Leclercq,

Ahmed,

Amadieu

et al. 2024

Preprint

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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.

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Differences in the serum metabolomic profile of progressive alcohol-related liver disease in comparison to non-progressive alcohol-related liver disease: a cross sectional metabolomics study

Puhakka,

Ahmed,

Haikonen

et al. 2024

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Alcohol-related liver disease (ALD) is a major cause of mortality and disability adjusted life years. It is not fully understood why a small proportion of patients develop progressive forms of ALD (e.g. fibrosis, cirrhosis). Differences in the metabolic processes could be behind the individual progression of ALD. Our aim was to examine differences in serum metabolome between patients with non-progressive ALD and patients with an early form of progressive ALD. The study had three study groups: progressive ALD (alcohol-related steatohepatitis or early-stage fibrosis, n=50), non-progressive ALD (simple steatosis, n=50) and healthy controls (n=32). Both ALD groups took part in a voluntary alcohol rehabilitation program. A non-targeted metabolomics analysis and targeted analysis of short chain fatty acids was done to the serum samples taken on the day of admission. We found 111 significantly (p<0.0005) altered identified metabolites between the study groups. Our main finding was that levels of glycine conjugated bile acids, glutamic acid, 7-methylguanine and several phosphatidylcholines were elevated in the progressive ALD group in comparison to both the non-progressive ALD group and the controls. Glycine conjugated bile acid, glutamic acid and 7-methylguanine also positively correlated with increased levels of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, cell death biomarker M65, and liver stiffness. Our results indicate that the enterohepatic cycle of glycine conjugated bile acids as well as lipid and energy metabolism are altered in early forms of progressive ALD. These metabolic processes could be a target for preventing progression of ALD.

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

Leclercq,

Ahmed,

Amadieu

et al. 2024

eLife

0

View full text Add to dashboard Cite

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 under the identification number NCT03803709.

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Alcohol use-associated alterations in the circulating metabolite profile in the general population and in individuals with major depressive disorder

Cited by 6 publications

References 43 publications

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

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

Differences in the serum metabolomic profile of progressive alcohol-related liver disease in comparison to non-progressive alcohol-related liver disease: a cross sectional metabolomics study

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

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