The investigation of alkylresorcinols has drawn an increasing interest recently. Alkylresorcinols (ARs) are natural chemical compounds synthesized by bacteria, fungi, sponges, and higher plants, possessing a lipophilic polyphenol structures and a myriad of biological properties. Human takes ARs as a component of a whole grain diet (from whole grain rye, wheat, and barley products), and thus, alkylresorcinols are frequently used as whole grain intake markers. Besides, ARs are considered as promising bioregulators of metabolic and immune processes, as well as adjuvant therapeutic agents for antimicrobial and anticancer treatment. In this review, we attempted to systematize the accumulated information concerning ARs origin, metabolism, biological properties, and their effect on human health.

The role of lactic acid (lactate) in cell metabolism has been significantly revised in recent decades. Initially, lactic acid was attributed to the role of a toxic end-product of metabolism, with its accumulation in the cell and extracellular space leading to acidosis, muscle pain, and other adverse effects. However, it has now become obvious that lactate is not only a universal fuel molecule and the main substrate for gluconeogenesis but also one of the most ancient metabolites, with a signaling function that has a wide range of regulatory activity. The Warburg effect, described 100 years ago (the intensification of glycolysis associated with high lactate production), which is characteristic of many malignant tumors, confirms the key role of lactate not only in physiological conditions but also in pathologies. The study of lactate’s role in the malignant transformation becomes more relevant in the light of the “atavistic theory of carcinogenesis,” which suggests that tumor cells return to a more primitive hereditary phenotype during microevolution. In this review, we attempt to summarize the accumulated knowledge about the functions of lactate in cell metabolism and its role in the process of carcinogenesis and to consider the possible evolutionary significance of the Warburg effect.

Aim. To assess the concentrations of bacterial and eukaryotic metabolites mainly involved in indole, kynurenine, and serotonin pathways of tryptophan metabolism in a cohort of patients with obesity. Materials and methods. Using high-performance liquid chromatography with mass spectrometric detection, the concentrations of several serum metabolites, such as kynurenine, kynurenic acid, anthranilic acid, xanthurenic acid, quinolinic acid, 5-hydroxyindole-3-acetate, tryptamine, serotonin, indole-3-lactate, indole-3-acetate, indole-3- butyrate, indole-3-carboxaldehyde, indole-3-acrylate, and indole-3-propionate, were analyzed in a cohort of obese patients compared with healthy volunteers.Results. It was found that serum levels of tryptophan metabolites of microbial and eukaryotic origin were significantly increased in obese patients. Therefore, the concentration of kynurenine in the blood serum in obese patients was 2,413 ± 855 nmol / l, while in healthy volunteers of the same age group, the level of kynurenine in the blood serum was 2,122 ± 863 nmol / l. In obese patients, two acids formed due to kynurenine metabolism; the concentrations of kynurenic and quinolinic acids were increased in the blood serum. The concentration of kynurenic acid in the blood serum in obese patients was 21.1 ± 9.26 nmol / l, and in healthy patients, it was 16.8 ± 8.37 nmol / l. At the same time, the level of quinolinic acid in the blood serum in obese patients was 73.1 ± 54.4 nmol / l and in healthy volunteers – 56.8 ± 34.1 nmol / l. Normally, the level of quinolinic acid is 3.4 times higher than the concentration of kynurenic acid, and in case of obesity, there is a comparable increase in these acids in the blood serum.From indole derivatives, mainly of microbial origin, the concentrations of indole-3-lactate, indole-3-butyrate, and indole-3-acetate were significantly increased in the blood serum of obese patients. In obese patients, the serum concentration of 5-hydroxyindole-3-acetate was elevated to 74.6 ± 75.8 nmol / l (in healthy volunteers – 59.4 ± 36.6 nmol / l); indole-3-lactate – to 523 ± 251 nmol / l (in healthy volunteers – 433 ± 208 nmol / l); indole-3-acetate – to 1,633 ± 1,166 nmol / l (in healthy volunteers – 1,186 ± 826 nmol / l); and indole-3-butyrate – to 4.61 ± 3.31 nmol / l (in healthy volunteers – 3.85 ± 2.51 nmol / l).Conclusion. In case of obesity, the utilization of tryptophan was intensified by both the microbiota population and the macroorganism. It was found that obese patients had higher concentrations of kynurenine, quinolinic and kynurenic acids, indole-3-acetate, indole-3-lactate, indole-3-butyrate, and 5-hydroxyindole-3-acetate. Apparently, against the background of increased production of proinflammatory cytokines by adipocytes in obese patients, the “kynurenine switch” was activated which contributed to subsequent overproduction of tryptophan metabolites involved in the immune function of the macroorganism.

Introduction. The concept of heterogeneity in obesity depending on the risk of developing cardiometabolic complications has garnered attention in recent decades, since not everyone with obesity goes on to develop metabolic dysfunction.The aim of the work is to study specific characteristics of colonic microbial communities in patients with different obesity phenotypes and in healthy individuals by employing metagenomics methods.Materials and methods. A total of 265 individuals (44 men and 221 women; mean age 47.1 ± 4.8 years) were enrolled in the study. They were further divided into clinical groups: Healthy normal-weight individuals (n = 129); patients with obesity (n = 136), including metabolically healthy obesity (n = 40) and metabolically unhealthy obesity (n = 55). Quantitative and qualitative assessment of the intestinal microbiome was based on metagenomic analysis. Fecal samples were used to isolate DNA and perform sequencing of the variable v3-v4 region of the 16S rRNA gene.Results. The study revealed statistically significant (p 0.05) differences between quantitative and qualitative variables in studied phylotypes of colonic microorganisms in healthy individuals without obesity and in patients with different obesity phenotypes.Discussion. Patients with obesity had higher levels of Bacteroidetes, Proteobacteria and lower levels of Actinobacteria, Firmicutes, TM7 (Saccharibacteria), Fusobacteria, and more frequently detected phyla Tenericutes, Planctomycetes and Lentisphaerae compared to healthy individuals. Metabolically healthy obese patients had more rarely detected phylum Lentisphaerae in their colonic microbiome, increased numbers of Firmicutes and reduced numbers of Bacteroidetes compared to metabolically unhealthy obese patients.Conclusion. The findings demonstrate alterations in the colonic microbiome in patients with different obesity phenotypes.

Alkylresorcinols (ARs) are polyphenolic compounds with a wide spectrum of biological activities and are potentially involved in the regulation of host metabolism. The present study aims to establish whether ARs can be produced by the human gut microbiota and to evaluate alterations in content in stool samples as well as metabolic activity of the gut microbiota of C57BL, db/db, and LDLR (−/−) mice according to diet specifications and olivetol (5-n-pentylresorcinol) supplementation to estimate the regulatory potential of ARs. Gas chromatography with mass spectrometric detection was used to quantitatively analyse AR levels in mouse stool samples; faecal microbiota transplantation (FMT) from human donors to germ-free mice was performed to determine whether the intestinal microbiota could produce AR molecules; metagenome sequencing analysis of the mouse gut microbiota followed by reconstruction of its metabolic activity was performed to investigate olivetol’s regulatory potential. A significant increase in the amounts of individual members of AR homologues in stool samples was revealed 14 days after FMT. Supplementation of 5-n-Pentylresorcinol to a regular diet influences the amounts of several ARs in the stool of C57BL/6 and LDLR (−/−) but not db/db mice, and caused a significant change in the predicted metabolic activity of the intestinal microbiota of C57BL/6 and LDLR (−/−) but not db/db mice. For the first time, we have shown that several ARs can be produced by the intestinal microbiota. Taking into account the dependence of AR levels in the gut on olivetol supplementation and microbiota metabolic activity, AR can be assumed to be potential quorum-sensing molecules, which also influence gut microbiota composition and host metabolism.