Gut Microbiota and its Metabolites in Pathogenesis of NAFLD

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

Aromatic Amino Acids: Phenylalanine and Tyrosine in Patients with Hypertension and Coronary Artery Disease

Aim. To evaluate changes in the profile of aromatic amino acids (AAA) in patients with cardiovascular diseases (CVD): hypertension and coronary artery disease (CАD) in comparison with healthy study participants.Material and methods. One hundred and thirty-one participants were included in the study: 58 participants were included in the hypertension group, 46 in the CАD group, and 27 participants without signs of CVD in the control group. We used ultrahigh-performance liquid chromatography in combination with a triple quadrupole analyzer to measure plasma AAA: phenylalanine and tyrosine (Phe, Tyr) in all study participants. The association of AAA with biochemical blood test parameters, echocardiography (EchoCG) parameters, blood pressure level and clinical characteristics was analyzed.Results. A statistically significant difference in the level of concentration of Phe and Tyr was revealed (p=0,002 and p=0,024, respectively), comparing the three groups. Post-hoc analysis showed differences in the circulating level of both amino acids in patients with CAD vs the control group (Phe p=0,008 and Tyr p=0,020). Also a statistically significant difference in the level of Phe of the hypertension and CАD groups (p=0,017) was found. A negative correlation of low-density lipoproteins (LDL) with the level of Phe (r=-0,685, p<0,05) and Tyr (r=-0,583, p<0,05), as well as the level of Phe with total cholesterol (r=-0,461, p<0,05) was found in the group without CVD. In the hypertension group, only a weak positive correlation was found between very low-density lipoproteins and AAA levels (Phe r=0,326 and Tyr r=0,365, p<0,05), while in patients with CAD, the level of Phe and Tyr was negative correlated with high-density lipoprotein (r=-0,378 and r=-0,543, respectively, p<0,05), and the level of Tyr with LDL (r=0,349, p<0,05). When isolating the group with proven atherosclerosis of peripheral and/or coronary arteries, a statistically significant difference was revealed between the group of patients with CVD and clinical and instrumental signs of atherosclerosis and the group of patients with CVD without proven atherosclerosis in Phe level (p=0,019).Conclusion. Concentrations of AAA were higher in patients with CVD, comparing with the control group. At the same time, an increase of the Phe level was associated with the presence of peripheral or coronary atherosclerosis. The revealed correlations of AAA with EchoCG parameters and lipid spectrum parameters require further study to understand the involvement of AAA in pathogenesis of CVD and its potential role as treatment target

Метаболизм триптофана при различном эффекте иммунотерапии немелкоклеточного рака легкого ингибиторами PD-1 / PD-L1

Introduction. In the structure of cancer incidence, lung cancer ranks first among men. In order to study the molecular mechanisms of the initiation and progression of lung cancer, it is necessary to study not only the tumor cells themselves, but also the features of the systemic tryptophan metabolism. Tryptophan catabolites, being to a large extent product of the metabolic activity of the intestinal microbiota, can affect the effectiveness of immunotherapy with checkpoint inhibitors. The kynurenine pathway of tryptophan metabolism is intensified in the body of cancer patients; its products have a pro-oncogenic and immunosuppressive effect, which may hinder the effectiveness of immunotherapy.Objective – to study the dynamics of changes in various metabolites of tryptophan metabolism in the blood serum and feces of patients with non-small cell lung cancer with various effects of immunotherapy with inhibitors of PD-1 (programmed cell death receptor 1) / PD-L1 (programmed cell death receptor 1 ligand).Materials and methods. The study included blood serum and stool samples obtained from 20 patients with non-small cell lung cancer treated with PD-1 / PD-L1 inhibitors. Using high-performance liquid chromatography with mass spectrometric analysis, the levels of 13 tryptophan metabolites were assessed in patients with various effects of immunotherapy. The significance of differences between the samples was assessed using a nonparametric method according to the Mann – Whitney test. They were considered statistically significant at p <0.05.Results. In fecal analyzes of patients in whom a positive effect of immunotherapy was observed, baseline levels of 5-hydroxyindole acetate and quinolinic acid were lower than in patients with tumor progression. Positive clinical dynamics was accompanied by a decrease in the content of indole-3-lactate, kynurenine and indole-3-carboxaldehyde in the feces of patients. In the serum of patients with a positive response, the initial content of 5-hydroxyindole acetate, indole-3-acetate, indole-3-butyrate and quinoline acid was lower than in patients with progression of non-small cell lung cancer. A positive response to immunotherapy was characterized by an increase in the levels of indole-3-butyrate and indole-3-propionate, and a negative response was not accompanied by statistically significant changes in the studied tryptophan metabolites.Conclusion. Profiling tryptophan metabolites in feces and serum of patients with non-small cell lung cancer can be used to predict the effectiveness of immunotherapy with PD-1 / PD-L1 inhibitors.Введение. В структуре онкологической заболеваемости рак легкого занимает 1-е место среди мужчин. С целью изучения молекулярных механизмов инициации и прогрессирования рака легких необходимо исследовать не только сами опухолевые клетки, но и особенности системного метаболизма триптофана. Катаболиты триптофана, будучи в большой степени продуктами метаболической активности микробиоты кишечника, могут влиять на эффективность проведения иммунотерапии ингибиторами контрольных точек. Кинурениновый путь метаболизма триптофана интенсифицируется в организме онкологических пациентов, его продукты имеют проонкогенное и иммуносупрессивное действие, что может препятствовать эффективности иммунотерапии.Цель исследования – изучение динамики изменений различных метаболитов триптофанового обмена в сыворотке крови и кале больных немелкоклеточным раком легкого при различных эффектах иммунотерапии ингибиторами PD-1 (рецептора программируемой клеточной гибели 1) / PD-L1 (лиганда рецептора программируемой клеточной гибели 1).Материалы и методы. В исследование были включены образцы сыворотки крови и кала, полученные от 20 больных немелкоклеточным раком легкого, получавших ингибиторы PD-1 / PD-L1. С помощью высокоэффективной жидкостной хроматографии с масс-спектрометрическим анализом проведена оценка уровней 13 метаболитов триптофана у больных с различными эффектами иммунотерапии. Достоверность различий между выборками оценивали с помощью непараметрического метода по критерию Манна–Уитни. Они считались статистически значимыми при р <0,05.Результаты. В анализах кала пациентов, у которых наблюдали положительный эффект от иммунотерапии, исходные уровни 5-гидроксииндолацетата и хинолиновой кислоты были ниже, чем у больных с прогрессированием опухоли. Положительная клиническая динамика сопровождалась снижением содержания индол-3-лактата, кинуренина и индол-3-карбоксальдегида в анализах кала больных. В сыворотке пациентов с положительным ответом исходное содержание 5-гидроксииндолацетата, индол-3-ацетата, индол-3-бутирата и хинолиновой кислоты оказалось ниже, чем у пациентов с прогрессированием немелкоклеточного рака легкого. Положительный ответ на иммунотерапию характеризовался повышением уровней индол-3-бутирата и индол-3-пропионата, а отрицательный – не сопровождался статистически значимыми изменениями исследованных триптофановых метаболитов.Заключение. Профилирование метаболитов триптофана в кале и сыворотке больных немелкоклеточным раком легкого может быть использовано для прогнозирования эффективности иммунотерапии ингибиторами PD-1 / PD-L1

«Кинурениновый переключатель» и ожирение

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. Цель. Изучить содержание метаболитов бактериального и эукариотического происхождения индольного, кинуренинового и серотонинового путей обмена триптофана у пациентов с ожирением.Материалы и методы. Методом высокоэффективной жидкостной хроматографии с масс-спектрометрическим детектированием изучили концентрации сывороточных метаболитов: кинуренина, кинуреновой кислоты, антраниловой кислоты, ксантуреновой кислоты, хинолиновой кислоты, 5-гидросииндол-3-ацетата, триптамина, серотонина, индол-3-лактата, индол-3-ацетата, индол-3-бутирата, индол-3-карбоксальдегида, индол-3-акрилата, индол-3-пропионата у пациентов с ожирением в сравнении с группой здоровых добровольцев.Результаты. Установлено, что у пациентов с ожирением в сыворотке крови статистически значимо повышен уровень метаболитов триптофанового обмена микробиотического и эукариотического происхождения. Концентрация кинуренина в сыворотке крови у больных с ожирением составляла 2 413 ± 855 нмоль/л, тогда как у здоровых добровольцев такой же возрастной группы – 2 122 ± 863 нмоль/л. Также у пациентов с ожирением в сыворотке крови были повышены две кислоты, которые образуются в результате метаболизма кинуренина – кинуреновая и хинолиновая. Концентрация кинуреновой кислоты в сыворотке крови у пациентов с ожирением составляла 21,1 ± 9,26 нмоль/л, а у здоровых 16,8 ± 8,37 нмоль/л соответственно. Тогда как концентрация хинолиновой кислоты в сыворотке крови при ожирении – 73,1 ± 54,4 нмоль/л, а у здоровых добровольцев – 56,8 ± 34,1 нмоль/л. В норме концентрация хинолиновой кислоты в 3,4 раза выше, чем концентрация кинуреновой кислоты, а при ожирении происходит сопоставимое их повышение. Из производных индола, которые имеют преимущественно микробиотическое происхождение, в сыворотке крови пациентов с ожирением статистически значимо повышена концентрация индол-3-лактата, индол-3-бутирата и индол-3-ацетата. У пациентов с ожирением концентрация в сыворотке крови метаболита серотонина – 5-гидроксииндол-3-ацетата – была повышена и составляла 74,6 ± 75,8 нмоль/л (у здоровых добровольцев – 59,4 ± 36,6 нмоль/л); индол-3-лактата – 523 ± 251 нмоль/л (у здоровых добровольцев 433 ± 208 нмоль/л); индол-3-ацетата – 1 633 ± 1166 нмоль/л (у здоровых добровольцев 1 186 ± 826 нмоль/л); индол-3-бутирата – 4,61 ± 3,31 нмоль/л (у здоровых добровольцев 3,85 ± 2,51 нмоль/л).Заключение. При ожирении происходит интенсификация утилизации триптофана как микробиотической популяцией кишечника, так и макроорганизмом. Установлено, что больные с ожирением имеют более высокие концентрации кинуренина, хинолиновой и кинуреновой кислот, индол-3-ацетата, индол-3-лактата, индол-3-бутирата и 5-гидроксииндол-3-ацетата. Видимо, на фоне гиперпродукции провоспалительных цитокинов адипоцитами у пациентов с ожирением срабатывает «кинурениновый переключатель», что и обеспечивает гиперпродукцию метаболитов триптофанового обмена, которые вовлечены в иммунологическую функцию макроорганизма.

Взаимосвязь хинолоновых регуляторов Pseudomonas aeruginosa и уровня иммуноглобулинов в крови больных раком легких

Introduction. Researchers in the field of oncology have a significant interest in the role of microorganisms in development of malignant neoplasms.Aim. To study the levels of 2-heptyl-3-hydroxy-4-quinolone (PQS) and 2-heptyl-4-quinolone (HHQ) produced by Pseudomonas aeruginosa in the blood of patients with lung cancer and to analyze the relation between their changes and changes in the level of immunoglobulins and vascular endothelial growth factor (VEGF) in the blood of patients with lung cancer.Materials and methods.  PQS and HHQ were quantified in the blood of patients using high performance liquid chromatography. The levels of immunoglobulins G (IgG),  secretory immunoglobulin A (s-IgA),  and VEGF in the blood were determined using ELISA.Results. Analysis have shown that the level of PQS in the blood of patients with lung cancer is 2-fold higher than in the control group. This change is accompanied by a decrease in the level of immunoglobulins IgG, as well as an increase in the content of s-IgA and growth factor VEGF in the blood.Conclusion. PQS level in the blood of patients with lung cancer is elevated creating conditions aggravating the course of the main disease and worsening its prognosis.Введение. Большой интерес у исследователей в области онкологии вызывает вопрос о роли микроорганизмов в развитии злокачественных новообразований.Цель исследования – изучить содержание 2-гептил-3-гидрокси-4-хинолона  (PQS) и 2-гептил-4-хинолона (HHQ), продуцируемых Pseudomonas aeruginosa, в крови больных раком легких и проанализировать взаимосвязь этого показателя с изменением уровня иммуноглобулинов и фактора роста эндотелия сосудов (vascular endothelial growth factor, VEGF) в крови.Материалы и методы. Выполнены количественное определение PQS и HHQ в крови больных с помощью высокоэффективной жидкостной хроматографии, а также анализ иммуноглобулинов класса G (IgG), секреторного иммуноглобулина а (s-IgA) и VEGF с помощью твердофазного иммуноферментного анализа.Результаты. Исследования показали, что уровень PQS в крови больных раком легких в 2 раза выше, чем у обследованных контрольной группы. На фоне данного сдвига наблюдаются снижение уровня иммуноглобулинов IgG, а также повышение содержания s-IgA и VEGF в крови.Заключение. У больных раком легких происходит повышение уровня PQS в крови, что формирует предпосылки для отягощения течения основного заболевания и ухудшения его прогноза

Changes of myocardial dysfunction and injury biomarkers over chemotherapy for multiple myeloma: difficulties in laboratory data interpretation

Aim. To study the changes of the levels of cardiac biomarkers (N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin I (hsTnI)) in patients with newly diagnosed multiple myeloma (MM) during programmatic treatment with bortezomib (VCd regimen).Material and methods. This prospective pilot study included patients with a newly diagnosed MM (n=30), who were scheduled for a cycle of chemotherapy including a proteasome inhibitor (bortezomib). All patients underwent standard laboratory (complete blood count, biochemical tests, serum protein electrophoresis), electrocardiography, echocardiography, as well as the level of specific laboratory markers of myocardial dysfunction (NT-proBNP) and injury (hsTnI) was determined immediately before treatment, after 3 and 6 cycles of chemotherapy.Results. The mean age was 63,8±10 years with a slight predominance of men (56,7%, n=17). The patients initially had an increased level of NT-proBNP (316 [75,9; 602,6] pg/mL) with its decrease to 144,0 [102,3; 294,0] pg/ml after 3 cycles and to 109,2 [59,9; 344,5] pg/ml after 6 cycles of chemotherapy. At the MM onset, the mean hsTnI values were 0,06 [0,03; 0,49] ng/mL, whereas after 3 and 6 chemotherapy cycles it accounted for 0,02 [0,01-0,68] and 0,65 [0,02; 1,51] ng/ml, respectively, with the normal range of less than 0,1 ng/ml. Despite this, no statistical significance has been obtained. There were no clinical and/or laboratory signs of heart failure, ischemia, or other non-cardiac causes of elevated NT-proBNP levels in this cohort. Multivariate regression analysis revealed the following significant factors influencing the initial hsTnI level: paraprotein, hemoglobin and erythrocyte sedimentation rate (ESR). The resulting regression model was characterized by a strong correlation (r=0,702, p<0,001).Conclusion. MM and its pathogenetic features such as paraproteinemia may be challenging for NT-proBNP and hsTnI levels assessment in group of interest before treatment. An unreliable assessment of these markers before chemotherapy may lead to incorrect baseline cardiovascular risk stratification and make it difficult for a cardiologist/cardio-oncologist to choose proper management strategy

New Russian antiarrhythmic agent nibentan: clinical effectiveness and pharmacokinetics in supraventricular arrhythmia management

Clinical effectiveness of a new Russian antiarrhythmic agent nibentan, Class III, was studied in various supraventricular arrhythmias. In total, 220 patients with atrial fibrillation (AF), atrial flutter (AFl), supraventricular tachycardia (SVT) and frequent supraventricular extrasystoles (SVE) were examined. ECG monitoring and echocardiography data, electrolyte balance and blood biochemistry were assessed. left ventricular myocardial kinetics and perfusion were studied by computed Tc-99 scintigraphy (Siemens-E. CAM camera, two detectors, 90 degree rotation, 16 gates per cardiac cycle; data analysis with 4DM sped program). Nibentan pharmacokinetics and pharmacodynamics, as well as its metabolite levels, were measured with highly effective chromatography-mass spectrometry. Nibentan was highly effective in various supraventricular arrhythmias, without affecting central hemodynamics or left ventricular perfusion. There was a positive correlation between nibentan administration time, its active metabolite detection, plasma Mg level increase, and QTinterval elongation. Conclusion: Nibentan, a new antiarrhythmic agent, is highly effective for supraventricular paroxysmal arrhythmias (AF, AFl, SVT) management. Due to long QT and ventricular tachycardia risk, nibentan should be administered at cardiac resuscitation departments or intensive care units only

In vivo and in vitro metabolism of the novel synthetic cannabinoid 5F-APINAC

Purpose New generations of synthetic cannabinoids (SCs) have recognized strong psychoactive effects, rapidly becoming potent drugs of abuse. Characterization of metabolites associated with SCs is useful for their subsequent detection in bio- logical samples. We aimed to investigate the metabolism of 5F-APINAC, a novel SC, in human liver microsomes (HLMs) (in vitro) and in a rat model (in vivo). Methods For the in vitro study, the standard solution of 5F-APINAC was incubated with HLMs for 1 h at 37 \ub0C. In the in vivo study, rats received 15 mg/kg of 5F-APINAC diluted in ethanol or in dimethyl sulfoxide, while a vehicle control group received placebo. Urine was collected 3, 6, and 24 h after administration. The metabolic characterization was performed using liquid chromatography\u2013ion trap mass spectrometry and liquid chromatography\u2013quadrupole time-of-flight mass spectrometry. Results In total, 15 metabolites associated with 5F-APINAC were tentatively identified. The metabolites were classified as: 1-adamantol metabolites, oxidative defluorination metabolites, and N-fluoropentylindazole-3-carboxylic acid metabolites. The modifications included ester hydrolysis, mono-, di-, and trihydroxylation of adamantyl ring and N-fluoropentylindazole moiety, oxidation (carbonyl formation) of the N-fluoropentyl side chain, oxidative loss of fluorine, and glucuronidation, as well as combinations thereof. The predominant metabolic reaction was ester hydrolysis in both in vitro and in vivo experi- ments and formation of M9 (5-fluoropentylindazole-3-carboxylic acid). However, the most recommendable metabolites for proving 5F-APINAC consumption in urine were M4.1, M7, and M13. No metabolites were detected in rat\u2019s urine 24 h after drug administration. Conclusions The discovered metabolites are proposed to be incorporated into routine screening analytical methods as the urine markers of 5F-APINAC consumption. This is the first report to demonstrate the metabolism of 5F-APINAC to our knowledge

A novel preliminary metabolomic panel for IHD diagnostics and pathogenesis

Abstract Cardiovascular disease (CVD) represents one of the main causes of mortality worldwide and nearly a half of it is related to ischemic heart disease (IHD). The article represents a comprehensive study on the diagnostics of IHD through the targeted metabolomic profiling and machine learning techniques. A total of 112 subjects were enrolled in the study, consisting of 76 IHD patients and 36 non-CVD subjects. Metabolomic profiling was conducted, involving the quantitative analysis of 87 endogenous metabolites in plasma. A novel regression method of age-adjustment correction of metabolomics data was developed. We identified 36 significantly changed metabolites which included increased cystathionine and dimethylglycine and the decreased ADMA and arginine. Tryptophan catabolism pathways showed significant alterations with increased levels of serotonin, intermediates of the kynurenine pathway and decreased intermediates of indole pathway. Amino acid profiles indicated elevated branched-chain amino acids and increased amino acid ratios. Short-chain acylcarnitines were reduced, while long-chain acylcarnitines were elevated. Based on these metabolites data, machine learning algorithms: logistic regression, support vector machine, decision trees, random forest, and gradient boosting, were used for IHD diagnostic models. Random forest demonstrated the highest accuracy with an AUC of 0.98. The metabolites Norepinephrine; Xanthurenic acid; Anthranilic acid; Serotonin; C6-DC; C14-OH; C16; C16-OH; GSG; Phenylalanine and Methionine were found to be significant and may serve as a novel preliminary panel for IHD diagnostics. Further studies are needed to confirm these findings

Alkylresorcinols as New Modulators of the Metabolic Activity of the Gut Microbiota

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