Host–Microbiota Interactions in Liver Inflammation and Cancer

Hepatocellular carcinoma (HCC) is a classical inflammation-promoted cancer that occurs in a setting of liver diseases, including nonalcoholic fatty liver disease (NAFLD) or alcoholic liver disease (ALD). These pathologies share key characteristics, notably intestinal dysbiosis, increased intestinal permeability and an imbalance in bile acids, choline, fatty acids and ethanol metabolites. Translocation of microbial- and danger-associated molecular patterns (MAMPs and DAMPs) from the gut to the liver elicits profound chronic inflammation, leading to severe hepatic injury and eventually HCC progression. In this review, we first describe how the gut and the liver communicate and discuss mechanisms by which the intestinal microbiota elicit hepatic inflammation and HCC. We focus on the role of microbial products, e.g., MAMPs, host inflammatory effectors and host–microbiome-derived metabolites in tumor-promoting mechanisms, including cell death and senescence. Last, we explore the potential of harnessing the microbiota to treat liver diseases and HCC.

Ethyl Glucuronide and Ethyl Sulphate in Urine: Caution in their use as markers of recent alcohol use

Aim To clarify the role of the ethanol metabolites, ethyl glucuronide (EtG) and ethyl sulfate (EtS), in monitoring alcohol consumption. Method We recruited 7 female and 17 male volunteers who were instructed to consume a quantity of beer (containing 48 gm ethanol) with food in one session. We examined urinary excretion of EtG and EtS over time and looked for correlations between the concentrations of the metabolites EtG and EtS. Results EtG concentrations in urine varied between 0.026 and 430.372 μg/ml with average values between 11.85 μg/ml (SD 19.75), 30 min after alcohol intake, and 100.39 μg/ml (SD 101.34), 4.5 h after alcohol intake. EtS urinary concentration ranged from 0.006 to 101.432 μg/ml with average values between 4.77 μg/ml (SD 5.42), 30 min after alcohol intake, and 30.14 μg/ml (SD 27.20), 4.5 h after alcohol intake. Spearman’s test showed that urinary EtG and EtS correlated significantly at several time points. Conclusion The great interindividual variability in their excretion suggests caution in the use of urinary measurement of these metabolites in forensic investigations.

Conversion of amino acids to aryl/heteroaryl ethanol metabolites using human CYP2D6-expressing live baker's yeast

Biotransformation of amino acids into aryl/heteroaryl ethanol metabolites using human CYP2D6 for developing a potential anti-depressant agent.

From Ethanol to Salsolinol: Role of Ethanol Metabolites in the Effects of Ethanol

In spite of the global reputation of ethanol as the psychopharmacologically active ingredient of alcoholic drinks, the neurobiological basis of the central effects of ethanol still presents some dark sides due to a number of unanswered questions related to both its precise mechanism of action and its metabolism. Accordingly, ethanol represents the interesting example of a compound whose actions cannot be explained as simply due to the involvement of a single receptor/neurotransmitter, a scenario further complicated by the robust evidence that two main metabolites, acetaldehyde and salsolinol, exert many effects similar to those of their parent compound. The present review recapitulates, in a perspective manner, the major and most recent advances that in the last decades boosted a significant growth in the understanding on the role of ethanol metabolism, in particular, in the neurobiological basis of its central effects.