The objective of this study was to investigate the metabolic activity of the gut microbiota in cirrhosis due to different variants of fatty liver disease (alcoholic vs. non-alcoholic [metabolic-associated] one [AFLD and MAFLD]). The present study included 24 patients with alcoholic liver cirrhosis, 16 patients with MAFLD-related cirrhosis, and 20 healthy controls. The level and spectrum of short-chain fatty acids (SCFAs) were determined via gas–liquid chromatography. All patients with cirrhosis showed a decrease in the total content of SCFAs (p < 0.001) and absolute content of acetate (p < 0.001), propionate (p < 0.001), butyrate (p < 0.001), and isovalerate (p < 0.001). In MAFLD cirrhosis, the metabolic activity of the microbiota was significantly altered compared to patients with alcoholic cirrhosis, as evidenced by a lower total SCFA content (p < 0.001) and absolute content of acetate (p < 0.001), propionate (p < 0.001), and butyrate (p < 0.001); a higher relative content of isovalerate (p < 0.001); and a higher IsoCn/Cn ratio (p < 0.001). Various clinical and laboratory parameters correlate differently with fecal SCFAs and their fractions in cirrhosis due to AFLD and MAFLD. SCFA-producing metabolic activity is reduced more in MAFLD cirrhosis than in alcoholic cirrhosis. According to the etiological factors of cirrhosis, disorders of this metabolic activity may be involved in different pathogenetic pathways.

The aim of this study was to investigate the levels of various tryptophan metabolites in patients with alcoholic liver disease (ALD) and metabolic-associated fatty liver disease (MAFLD) at different stages of the disease. The present study included 44 patients diagnosed with MAFLD, 40 patients diagnosed with ALD, and 14 healthy individuals in the control group. The levels of tryptophan and its 16 metabolites (3-OH anthranilic acid, 5-hydroxytryptophan, 5-methoxytryptamine, 6-hydroxymelatonin, indole-3-acetic acid, indole-3-butyric, indole-3-carboxaldehyde, indole-3-lactic acid, indole-3-propionic acid, kynurenic acid, kynurenine, melatonin, quinolinic acid, serotonin, tryptamine, and xanthurenic acid) in the serum were determined via high-performance liquid chromatography and tandem mass spectrometry. In patients with cirrhosis resulting from MAFLD and ALD, there are significant divergent changes in the serotonin and kynurenine pathways of tryptophan catabolism as the disease progresses. All patients with cirrhosis showed a decrease in serotonin levels (^MAFLDp = 0.038; ^ALDp < 0.001) and an increase in kynurenine levels (^MAFLDp = 0.032; ^ALDp = 0.010). A negative correlation has been established between serotonin levels and the FIB-4 index (p < 0.001). The decrease in serotonin pathway metabolites was associated with manifestations of portal hypertension (p = 0.026), the development of hepatocellular insufficiency (p = 0.008) (hypoalbuminemia; hypocoagulation), and jaundice (p < 0.001), while changes in the kynurenine pathway metabolite xanthurenic acid were associated with the development of hepatic encephalopathy (p = 0.044). Depending on the etiological factors of cirrhosis, disturbances in the metabolic profile may be involved in various pathogenetic pathways.

The aim of this study was to investigate the short-chain fatty acid (SCFA) activity of the gut microbiota of patients with metabolic-associated fatty liver disease (MAFLD). The level and spectrum of short-chain fatty acids (SCFAs) were determined via gas–liquid chromatography. Liver fibrosis was assessed using the FIB-4 index and elastography. Among 42 non-cirrhotic MAFLD patients, 24 had high fecal SCFA levels (group H) and 18 had low fecal SCFA levels (group L). Patients in group H had lower serum uric acid, total cholesterol, and LDL cholesterol levels but a higher BMI than those in group L. All patients in group L and only 37.9% of those in group H were found to have hypercholesterolemia. In patients with hypercholesterolemia, the level of SCFAs was lower than that in patients without hypercholesterolemia. Patients in group H had less liver fibrosis than patients in group L. A total of 50.0% of the patients in group H and 92.3% of those in group L had significant liver fibrosis (≥F2). Patients with significant liver fibrosis had lower levels of fecal SCFAs—particularly acetate and butyrate. The fecal SCFA levels were positively correlated with gamma-glutamyl transferase, total bilirubin levels, BMI, and platelet count and were negatively correlated with FIB-4, liver stiffness, serum total, and LDL cholesterol levels.

Aim: to provide information on the results of recent scientific research in the field of non-alcoholic fatty liver disease (NAFLD) metabolomic profiling.Key points. Metabolites of microbial origin are important biological molecules involved in many specific reactions of the human body. This literature review presents the results of recent studies in the field of metabolomics in patients with NAFLD. A more detailed understanding of the role of individual metabolites or their combinations in the NAFLD pathogenesis will allow us to determine the vector of further diagnostic and therapeutic approaches for this nosology. The research results of the probiotics effect on the levels of certain metabolites are currently being discussed.Conclusion. New research data in the field of studying the human metabolomic profile are presented. The results allow us to summarize the effects of microbial agents and their metabolites in the formation of changes in the liver parenchyma in the context of NAFLD. Changes in the level of endogenous ethanol, secondary bile acids, aromatic amino acids, branched chain amino acids, etc. have been described. Correlation between metabolites and certain bacterial strains has been established. A correlation between the ratio of bacteria types and clinical/laboratory parameters was noted in patients taking prebiotics.

   Aim: to study the metabolic activity of the intestinal microbiota depending on the stage of metabolic dysfunction-associated fatty liver disease (MAFLD).   Materials and methods. The study included 85 patients with MAFLD (27 patients with steatosis without steatohepatitis and fibrosis, 42 patients with steatohepatitis, 16 patients with cirrhosis as an outcome of MAFLD, Child — Pugh class A–B) and 20 healthy people who formed the control group. The level and spectrum of short-chain fatty acids (SCFA) were determined by gas-liquid chromatography.   Results. It was found that patients with MAFLD at the stage of steatosis and cirrhosis of the liver have unidirectional changes in the metabolic activity of the intestinal microbiota. We established a decrease in the absolute concentrations of SCFA — their total content, the level of acetate, propionate, butyrate, a decrease in the level of isoacids. The SCFA profiles showed an increase in the proportion of acetate and a decrease in propionate and butyrate. Moreover, changes in the named parameters of SCFAs are aggravated with progression to liver cirrhosis. At the stage of steatohepatitis, we identified two subgroups of patients with different levels of metabolic activity of the microbiota. Patients whose microbiota metabolism for SCFA production was high had correspondingly elevated SCFA levels. And, on the contrary, patients in whom the metabolic activity of the microbiota was reduced were characterized by a steady decrease in SCFAs and disease progression to liver cirrhosis. In the study, we showed an inverse correlation between the calculated prognostic indices of NFS and FIB-4, elastography values with the total level of SCFA, the level of acetate, propionate, butyrate. Thus, a decrease in the content of SCFA for patients with MAFLD can be considered as a prognostic marker of an unfavorable course of liver disease.

Aim. This review will demonstrate possibilities of using metabolomic profiling to identify biomarkers of various internal organs diseases.Key points. A new diagnostic direction is associated with high-sensitive spectral analysis of biomarker molecules. This review will discuss some of the latest advances with an emphasis on the use of metabolomics to identify major metabolic changes in various diseases. The possibility of finding diagnostic markers in diseases of the gastrointestinal tract, respiratory and cardiovascular systems, in oncology, endocrinology, neurology are discussed. These results define new potential therapeutic strategies, making metabolomics useful for a wide range of biomedical and pharmaceutical research.Conclusion. Metabolomic profile changes in different types of diseases will help to improve understanding of the pathogenesis. New therapeutic approaches may be developed. They will take into account individual characteristics of the patient, identified by using current molecular technologies. The results of metabolomic studies can be used to monitor treatment outcomes.