The review deals with the role of aromatic amino acids and their microbial metabolites in the development and progression of non-alcoholic fatty liver disease (NAFLD). Pathological changes typical for NAFLD, as well as abnormal composition and/or functional activity of gut microbiota, results in abnormal aromatic amino acid metabolism. The authors discuss the potential of these amino acids and their bacterial metabolites to produce both negative and positive impact on the main steps of NAFLD pathophysiology, such as lipogenesis and inflammation, as well as on the liver functions through regulation of the intestinal barrier and microbiota-gut-liver axis signaling. The review gives detailed description of the mechanism of biological activity of tryptophan and its derivatives (indole, tryptamine, indole-lactic, indole-propyonic, indole-acetic acids, and indole-3-aldehyde) through the activation of aryl hydrocarbon receptor (AhR), preventing the development of liver steatosis. Bacteria-produced phenyl-alanine metabolites could promote liver steatosis (phenyl acetic and phenyl lactic acids) or, on the contrary, could reduce liver inflammation and increase insulin sensitivity (phenyl propionic acid). Tyramine, para-cumarate, 4-hydroxyphenylacetic acids, being by-products of bacterial catabolism of tyrosine, can prevent NAFLD, whereas para-cresol and phenol accelerate the progression of NAFLD by damaging the barrier properties of intestinal epithelium. Abnormalities in bacterial catabolism of tyrosine, leading to its excess, stimulate fatty acid synthesis and promote lipid infiltration of the liver. The authors emphasize a close interplay between bacterial metabolism of aromatic amino acids by gut microbiota and the functioning of the human body. They hypothesize that microbial metabolites of aromatic amino acids may represent not only therapeutic targets or non-invasive biomarkers, but also serve as bioactive agents for NAFLD treatment and prevention.

Diagnosis of liver disease in particular non-alcoholic fatty liver disease (NAFLD) is largely determined by methods that are informative, safe, non-invasive, highly sensitive and can be used in all patients without exception. One of these methods is gas chromatography-mass spectrometry (GC-MS). Our study presents the results of serum metabolome assessment by the GC-MS method in male patients for the diagnosis of NAFLD at the stage of non-alcoholic steatohepatitis. In serum samples obtained from 25 patients, 319 compounds were identified, among them 109 were annotated. In patients with NAFLD, there was a significant increase in indole carboxylic and fatty acids, hypoxanthine, hydroxycarboxylic and phenylcarboxylic acids. The results of the study showed that low-molecular metabolites in particular reduced levels of 4-hydroxybutyric acid and 360 compounds suggests possible influence of metabolites on the pathogenesis of NAFLD, and an elevated level of sugar alcohol suggests a possible damaging effect on liver cells. For the detected compounds 4-hydroxybutyric acid, compound-360 and sugar alcohol, high specificity and sensitivity values, high confidence intervals and AUC values were shown, which indicates the possibility of using mass spectrometry analysis of plasma metabolome at high levels of steatohepatitis with high degree of reliability and probability.