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The aim of the study: to summarize the study results on the interaction between intestinal microbiota and the human body in terms of the risk for dyslipidemia and cardiovascular system diseases. Material and methods. A descriptive and comparative study was conducted based on the analysis of scientific literature focused on the role of intestinal microbiota in the occurrence of dyslipidemia and the development of cardiovascular diseases. The following research methods were used: search, comparative, analysis of scientific literature, generalization, synthesis. Results. Gut microbiota plays an important role in maintaining health, and its pathology contributes to the risk for cardiovascular diseases. In some cases, monitoring the intestinal microbiota and the preventive use of pre- and probiotics can reduce the risk for developing cardiovascular system diseases. Conclusions. It has been found that trimethylamine-N-oxide, a microbiota-dependent metabolite, is the first of many existing bacterial products with the proven role in the development of cardiovascular system diseases.

Aim: To summarize the state-of-the-art data on the molecular mechanisms of bile acid (BA) synthesis and absorption, their impaired absorption and receptor-dependent signaling, as well as on the effects of the gut microbiota on BA metabolism in inflammatory bowel diseases (IBD). Key messages: BA malabsorption is one of the relevant mechanisms in the development of diarrhea in IBD. It may occur due to various disorders of the ileum, such as terminal ileitis, ileocolitis or ileocecal resection in Crohn's disease and ileoanal reservoir in ulcerative colitis. Molecular mechanisms of BA malabsorption in IBD are related to a defect in the BA uptake by the apical sodium dependent bile acid transporter (ASBT), as well as to a decrease in the expression of pregnane X receptor (PXR) and farnesoid X receptor (FXR), whose activation by glucocorticoids results in an increase in the BA reabsorption in the ileum and a decrease in hologenic diarrhea. The metabolic profile of luminal BA in IBD is characterized by an increased content of conjugated and 3-OH-sulfated BA and reduced levels of secondary BA. The decrease in the relative abundance of the Lachnospiraceae and Oscillospiraceae spp. in IBD patients leads to a decrease in the efficiency of microbial biotransformation of BA. Changes in the BA metabolic profile in IBD affect the gut microbiota, and impaired interaction with the FXR, PXR, G protein-coupled bile acid receptor (GPBAR1), retinoid-related orphan receptors (RORs) and vitamin D receptor (VDR) results in a pro-inflammatory response and increased intestinal permeability, bacterial translocation, and IBD progression. BA metabolism in IBD-associated primary sclerosing cholangitis (PSC-IBD) is characterized by a significant decrease in the luminal BA pool, and the microbiota composition is remarkable for an increase in the relative abundance of Fusobacterium and Ruminococcus spp., and a decrease in Veillonella, Dorea, Blautia, Lachnospira and Roseburia. Conclusion: Disordered synergistic interplay of BA with intestinal microbiota results in disruption of the ligand-receptor interaction and BA metabolic transformation, which contributes to the activation of the immune system, formation of a vicious circle of chronic inflammation and IBD progression. Further studies into mutual influence of the gut microbiota, BA metabolism and receptor signaling may promote the development of new methods for the diagnosis and treatment of IBD.

Background: Secondary immunodeficiency in recipients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the pediatric practice is often accompanied by bacterial and viral infections of the gastrointestinal tract (GIT), resistant to conventional therapy. Fecal microbiota transplantation (FMT) promotes intestinal recolonization and eradication of gastrointestinal symptoms. Clinical case description: A 2.5-year-old patient underwent allo-HSCT from a haploidentical related donor (father) as a part of the treatment of acute myeloid leukemia. A month after the last procedure, diarrhea (up to 10 times a day) and abdominal pain appeared. The astrovirus RNA and Clostridium difficile toxin A were detected in the feces. The FMT was prescribed. After two FMT procedures, the intestinal syndrome leveled out, and the tests for the astrovirus RNA and clostridial toxins were negative. The content of cholic and, in particular, deoxycholic acids, as well as their conjugates with glycine and taurine, in the feces increased; the acetic acid content increased with a simultaneous decrease in the level of propionic acid, which indicates the restoration of the intestinal microbiotas functional potential. Conclusion: FMT contributes to the restoration of the normal intestinal microflora, the elimination of clostridial toxins, enteroinvasive E. coli and astrovirus infection in allo-HSCT recipients, as evidenced by the indicators of the intestinal microbiota activity, and can be used in allo-HSCT recipients with infections refractory to conventional therapy.

Today, the positive impact of bariatric surgery on the course of type 2 diabetes mellitus has been studied in detail. At the same time, not only the effect of direct weight loss and the incretin theory, but also other mechanisms for normalizing glycemia are being actively discussed. Thus, special attention is paid to the metabolism of bile acids and their influence on various indicators of homeostasis, including carbohydrate metabolism. After bariatric interventions of the bypass type, the passage of bile through the gastrointestinal tract, as well as its interaction with food masses, changes significantly, which served as the basis for studying this phenomenon. The information accumulated to date indicates enormous changes occurring not only in the anatomy, but also in the biology of the gastrointestinal tract after bariatric bypass surgery. The composition of the intestinal microbiota and the composition of bile masses undergo significant changes. Most of the works available today suggest that these changes are the cause of a number of metabolic rearrangements, and directly affect carbohydrate metabolism. This issue is still under study and accumulation of the necessary information, but today it can be stated with confidence that the role of bile passage, bile acid circulation and restructuring of the intestinal microbiota in the regulation of carbohydrate metabolism and energy balance after bariatric bypass surgery is of extreme importance.

The creation of a highly effective model for diagnosing liver diseases of various genesis (including subclinical forms) in animals is one of the most urgent problems of veterinary science. Currently, there is a need to create more specific than "classical" tests for a clear differentiation of various pathologies of the hepatobiliary system, including diseases characterized by the absence of pathognomonic clinical or laboratory signs. One of the extremely promising predictors of such pathologies is bile acids (BA) and their pool. The main goal of the study is to search and analyze information from scientific publications dedicated to the study of the BA’s pool in various animal species, its changes in various pathologies of the hepatobiliary system and its diagnostic value. In English and Russian, in accordance with the recommendations of H. Snyder, various bibliographic databases (Elibrary, Pubmed, Scopus (Elsevier), Web of Science (Clarivat)) were searched for thematic publications by keywords with further highlighting the most cited ones. Articles published before 2015 were used only if they contained information critical to the better understanding of the topic, or it was not found in later publications. Based on the literature analysis, it can be concluded that liver diseases affect the synthesis and metabolism of bile acids. Therefore, BAs separately and their pool are studied and utilized as diagnostic and prognostic markers. However, it is not yet clear how the etiology of liver diseases affects the composition of bile acids. It should also be noted that in different animals there are differences in the BA pool, as well as in the details of their metabolism. This indicates differences in the specificity, affinity, and activity of enzymes involved in BA synthesis. Thus, BAs also affect the etiopathogenesis of diseases of the hepatobiliary system differently for each animal species, and, conversely, etiopathogenetic factors change the pool of BAs depending on the individual characteristics of the species.

Aim. A review to highlight the bile acids importance as steroid mediators of nervous system activity and show the nervous system involvement in cholesterol metabolism and bile acids production.Key points. Presence of bile acid membrane and nuclear receptors and their activation role in mediating manifold metabolic processes have been established in various organs and tissues. Bile acid transporters are discovered in CNS. The animal brain under physiological conditions was found to contain about 20 bile acid types of likely innate origin suggested by their high contents; the bile acids spectrum in CNS differs significantly from blood plasma. Clinical and experimental works are conclusive about the CNS bile acids influence on mitochondrial membrane, their antioxidative role and, probably, steroid-mediator involvement in indirect regulation of memory, attention, motor functions and appetite.Conclusion. Bile acids act as pleiotropic signalling molecules affecting various tissues. The presence in CNS of various bile acid synthesis-related receptors and enzymes indicates their value in brain functioning and warrants research into their metabolism.

It has been epidemiologically established that the rate of primary cholangiocarcinomas increases greatly in the ObIrtysh basin which is hyperendemic for helminth Opisthorchis felineus in comparison with other regions where the population is not infested. In this connection chronic opisthorchiasis is considered as facultative liver precancer. The study of cholangiocarcinogenesis mechanisms will allow developing pathogenetic approaches to prevention of this tumor. Aim of the study was to investigate the significance of microbiota of the hepatobiliary tract of chronic opisthorchiasis patients in changing of biochemical composition of bile and investigation of its biological influence on somatic cells membrane. Material and methods. Objects of research: bacteria; inbred mice infected by opisthorchis; samples of bile, cultures of human embryo fibroblasts and splenocytes of inbred mice in vitro; blood plasma; standard primary and secondary bile acids. We studied: species of bacteria colonizing bile ducts; quantitative and qualitative composition of bile acids, and level of diene conjugates and malondialdehyde in duct bile samples; biological activity of bile on processes of lipid peroxidation of cell membranes in vitro; influence of bile and lipid peroxidation products on cytomembrane permeability; activity of antioxidant systems of the body. Results and discussion. It was found out, that bile of patients with chronic opisthorchiasis in majority of cases (77.0 %) was infected by different species of bacteria. In 30.0 % of cases certain types of intestinal bacteria (Proteus vulgaris, P. mirabilis, Citrobacter freundii, Bacteroides alcaligues faecalis, Clostridium, Streptococcus faecalis, Escherichia coli) change biochemical composition of duct bile – deconjugated primary and secondary bile acids and also high level of total bile acids are detected. Bile of the above biochemical composition, against the background of depletion of antioxidant system, induces activation of cell membrane lipid peroxidation processes and significantly increases their permeability to toxic components of bile. These processes are promotor in cholangiocarcinogenesis.

Obesity and functional bowel disease (FBD) are affecting a large number of people worldwide. They have psychosocial consequences and associated with considerable healthcare resource use. The purpose of this review was a comprehensive study of the relationship between obesity and FBD, as well as mechanisms to explain this relationship. An analysis of the literature provides strong evidence of a link between obesity and diarrhea, but there is currently insufficient data to speak confidently about the link between obesity and irritable bowel syndrome. Most studies suggest that adult obesity is not associated or negatively associated with constipation. The association of obesity with diarrhea is most convincingly explained through diet, eating behavior, changes in the metabolism of bile acids, accelerated colonic transit, altered intestinal microbiota and associated inflammation and increased intestinal permeability. Medicines taken by patients, as well as non-alcoholic fatty liver disease, can play their own role.Planning and conducting studies, including longitudinal ones, based on valid diagnostic criteria and taking into account the widest possible range of confounders, will allow a deeper study of the problem of comorbidity of obesity and FBD. This will help optimize the treatment of these diseases.

The occurrence of chronic diarrhea after cholecystectomy (CCY) has been described by many researchers. However, the main mechanisms of the development of this diarrhea are not fully understood. Supposed that dysregulation of the bile acids (ВA) absorption in the ileum is played a significant role in the development of diarrhea syndrome. Aim. To determine the role of the fibroblast growth factor 19 (FGF19) level in the serum and BA concentration in feces in pathogenesis of bile acid diarrhea (ВАD) in patients after CCY. Materials and methods. Sixty-one patients were examined at various times after CCY: 30 patients with chronic diarrhea that appeared after CCY (group 1) and 31 patients with normal stools (group 2). In all patients, the level of FGF19 in the blood serum, and the daily excretion of BA in the feces were studied. The control group consisted of 28 healthy individuals. Results. In the 1st group we found lower concentrations of FGF19 in the blood serum 86.2 ng/ml (67.8; 117.8) compared with concentrations in the 2nd group 259 ng/ml (170.6; 318.8), p0.001. The daily excretion of bile acids with feces in the 1st group was 657.4 mg/day (524.6; 830.1), which was twice more than in the 2nd group and the control group. It was established an inverse correlation between serum concentration of the FGF19 and the BA excretion in the feces in all examined patients. It indicates a possible relationship between the low concentration of FGF19 in blood serum and malabsorption of the BA. Conclusion. Low level of FGF19 in the blood serum and a high excretion of BA in the feces may be one of the causes of BAD in patients undergoing cholecystectomy. Our results indicate the important role of FGF19 in the development of chronic diarrhea, which can be considered as one of the variants of postcholecystectomy syndrome.

Bile acids were first considered carcinogenic in 1939. Since then, accumulated data have associated colon cell changes with high levels of bile acids as an important risk factor for developing colorectal cancer, which is more common among people who consume large amounts of dietary fat. Secondary bile acids formed under the influence of the intestinal microbiota can cause the formation of reactive forms of oxygen and nitrogen, disruption of the cell membrane, mitochondria, DNA damage, reduction of apoptosis, increased cell mutation, turning them into cancer cells. High-fat diet, intestinal microflora, bile acids are a risk factors for colorectal cancer.

Introduction. Traumatism is one of the most current problems nowadays. Its increase is caused by the escalation in number of emergencies. In recent years the proliferation of frequency of terrorist attacks and local armed conflicts has been observed. Under those circumstances, the acute blood loss is considered to be the leading cause of injured people’s death. An effective way of stopping a massive external haemorrhage from the limbs is applying the tourniquet which entirely ceases arterial blood flow. It is deemed that safe duration of tourniquet application is two hours. Individual authors’ researches indicate the negative impact of post-tourniquet reperfusion on body. However, influence of the acute blood loss, which is complicated by limb ischemia-reperfusion, on the internal organs is insufficiently studied. Objective of research: to establish peculiarities of the functional state of the liver under impact of two-hour tourniquet limb ischemia and acute blood loss in the experiment. Materials of the research and their discussion. The experiments were conducted on 96 non-linear male rats weighing 200-220g. All animals were divided into four groups: control and three experimental ones. Injuries were inflicted under thiopental l- sodium anesthesia. In the first experimental group, the limb ischemia-reperfusion injury was performed on animals by a method of applying a band of an elastic tourniquet SWAT-T. (USA), the width of 10 mm, proximally to the rat’s left paw for 120 minutes. Acute blood loss (20% of circulating blood volume) was performed by severing a femoral vein in the second experimental group. In the third experimental group, these lesions were combined. The control group included the animals, which were injected into anesthesia and subsequently were used for investigations in an hour. An hour and two hours later, as well as in 1, 7 and 14 days, the functional state of the liver was determined in experimental animals through collecting the bile within an hour with a further determination of the total bile acids concentration, the cholesterol and calculation of the cholate-cholesterol coefficient. Result of the research and their discussion. It was established that the two-hour exsanguination of the limb in the reperfusion period can negatively affect the functional state of the liver with a maximum of abnormalities after 3 hours. In comparison with the control group, the content of total bile acids in the bile appreciably decreased and the cholate-cholesterol coefficient increased. Under the circumstances of the acute bleeding, the abnormalities were significantly greater. The reduction in the content of the total bile acids in bile and the cholate-cholesterol ratio was perceived at all periods of the observation as well as the increase in the content of the cholesterol after 1 and 7 days of the experiment, which indicate the dysfunctions in process of the bile acids synthesis from cholesterol and the amplification in lithogenic characteristics of bile. For the first time, it was shown that the combination of acute blood loss and limb ischemia-reperfusion exacerbated the dysfunction of functional state of the liver. Besides, a greater decrease in the content of total bile acids in bile, particularly in 3 hours, in 1 and 14 days of experiment, a significant increase in cholesterol content and a reduction in cholate-cholesterol coefficient after three hours of reperfusion period were observed. Consequently, the two-hour tourniquet application in the condition of the acute blood loss in the amount of 20% of circulating blood volume aggravates the liver dysfunction in comparison to each of the effects in particular. This should be taken into consideration while assisting injured and affected people with acute blood loss from limbs, who were being applied with tourniquet. Our results aim at searching for efficacious tools of counteracting the impact of limb ischemia-reperfusion in conditions of acute blood loss. Conclusions. The complication of acute blood loss by limb ischemia-reperfusion is accompanied by a summation of their negative impact on the functional state of the liver with a maximum value after 3 h - 1 day of the experiment. Under these circumstances, in 3 hours, 1 and 14 days the content of total bile acids in bile is statistically probably lower compared to the experimental group in which the acute blood loss was solely performed. The increase in the content of the cholesterol in bile is observed as well as the reduction in cholesterol ratio that are statistically substantial after 3 hours of the experiment.

The mechanisms of epileptiform neuronal activity development under blood-brain barrier (BBB) dysfunction remains relevant in modern psychoneurology. In the present work we mimic some effects of BBB disruption in the culture of hippocampal neurons to examined the effect of serum-adapted ionic environment on the impulse activity of hippocampal neurons and the role of serum protein thrombin in induction of epileptiform neuronal activity. Using the whole-cell patchclamp method under current-clamp mode we analyzed the spontaneous action potentials (AP) in the single hippocampal neurons. The changing of ionic extracellular neuronal environment to such serum-adapted contributed to the development of epileptiform tonic activity of cultured hippocampal neurons and led to increase the average APs frequency by 65.1 ± 17.9% (n = 5) in neurons with spontaneous firing activity (FA) and to occurrence of tonic electrical activity (1.65 ± 0.4 s-1) in neurons without firing activity. Glutamate NMDA receptors significantly contribute to epileptiform tonic activity formation in neurons with FA, while their role in tonic activity providing in neurons without FA was insignificant. Thrombin (5 U/ml) in the serum-adapted ionic solution significantly enhanced of epileptiform activity in neurons with and without spontaneous FA: APs frequency increased in these neuronal groups by 117.3 ± 25.6% (n = 3) and by 61.8 ± 11.5% (n = 3), respectively, compared with that in the serum-adapted ionic solution only. Blockade of thrombin protease activated receptor 1 (PAR-1) by application of SCH 79797 (10 μm) canceled the thrombin's effect in neurons without spontaneous FA, and significantly reduced such in neurons with FA. Therefore, the change of ionic extracellular neuronal environment to serum-adapted stimulates the occurrence of epileptiform activity in hippocampal neurons, that is apparently associated with NMDAreceptors activation in neurons with FA. The proepileptiform action of thrombin was mostly mediated by PAR-1 activation. Thrombin-dependent regulation of the hippocampal single neurons firing activity involves the mechanisms different from the modulation of glutamate NMDA receptors in these cells. [ABSTRACT FROM AUTHOR]

The article reflects current literature data on the epidemiology and risk factors of non - alcoholic fatty liver disease. An important aspect is the description of the modern views of combined lesions of the hepatobiliary tract and small intestine. Disorders of the intestinal microbiota play a special role in the development of non - alcoholic fatty liver disease. The value of enterohepatic circulation of bile acids in the development of intestinal and liver diseases was shown. It seems relevant to further study the comorbidity of the development of non - alcoholic fatty liver disease and enteropathy for the development of pathogenetically substantiated therapy.

Cancers of the gastrointestinal tract are widespread among the population and cause significant damage to the health care system. In order to improve the strategy of preventive measures and the detection of oncological diseases at the early stages, it is necessary to provide timely impact on possible risk factors contributing to the onset and progression of malignant neoplasms. This review demonstrates the association between the pathology of the biliary tract and oncological diseases of the digestive system, discusses the possible mechanisms of the influence of cholelithiasis and cholecystectomy on the development of malignant neoplasms of various parts of the gastrointestinal tract.

The role of duodenogastric reflux (DGR) in malignant degeneration of the gastric mucosa. It was demonstrated by immunohistochemistry using monoclonal antibodies to p53, PCNA, CD10, MUC2, MUC5AC, MUC6, CD31 and the polymerase chain reaction to detect CDX1, CDX2, FXR genes. The main carcinogenic components of bile are lysolecithin and conjugated bile acids. Biliary reflux increases the risk of malignant tumors in combination with Helicobacter pylori. DGR is one of the etiological factors for gastric cancer, so it determines the necessity for detailed diagnosis in clinical practice.

Along with the great progress in the fight against malignant neoplasms through the improvement of surgical care and the development of chemotherapy, the search for strategies and opportunities to prevent cancer is becoming increasingly important and promising. Early detection and rational treatment of chronic precancerous diseases must be a priority. In this regard, the possible role of ursodeoxycholic acid (UDCA, ursosan, etc.) has been closely studied in recent years. An overview of the role of ursodeoxycholic acid (UDCA) in the prevention of cancer is presented. The pathogenetic basis of this action is the proven normalizing effect of UDCA on bile acid metabolism, microbiome condition and apoptosis. The paper summarizes the latest data on the ability of UDCA to withstand malignization in the liver, throughout the gastrointestinal tract and beyond. These numerous experimental and clinical studies allow us to assert that UDCA drugs, except for the well-known and versatile hepatoprotective effect, can be considered as effective and promising means of cancer prevention throughout the digestive tract and associated organs. Further research into the broad spectrum of UDCA’s ability to prevent gastrointestinal malignization and beyond is reasonable and promising.

Aim. Сomparative studying of changes in the spectrum of bile acids in bile in patients with nonalcoholic fatty liver disease and cholelithiasis. Materials and methods. 140 patients were included in the survey: 50 - with nonalcoholic fatty liver disease and 90 - with cholelithiasis. The diagnosis of nonalcoholic fatty liver disease was established on the basis of ultrasound examination of the liver, the elasticity and fibrosis of liver by using the sonoelastography and liver biopsy. The prestone stage of cholelithiasis was established on the basis of ultrasound examination of the gallbladder and biochemical examination of bile. The level of total cholesterol, triglycerides, alanine aminotransferase, aspartate aminotransferase, total bilirubin, alkaline phosphatase and gamma glutamyl transpeptidase were studied using the analyzer "Labsystems" (Finland). The spectrum of bile acids in bile is studied by mass spectrometry on AmazonX apparatus (Bruker Daltonik GmbH, Bremen, Germany). Results and discussion. Biochemical blood test revealed increase of cholesterol, triglycerides, cytolysis markers, and cholestasis, the most pronounced in patients with nonalcoholic fatty liver disease. Biochemical study of bile showed increase of cholesterol, decrease the total amount of bile acids and cholatecholesterol coefficient in the vesicle and hepatic bile in patients with nonalcoholic fatty liver disease and cholelithiasis. Mass spectrometry showed decrease the total amount of free bile acids (choloidal, chenodeoxycholic, deoxycholic) and increase the content of conjugated bile acids (glycocholic, glycodesoxycholic, taurocholic, taurodeoxycholic, ursodeoxycholic), the most pronounced in patients with nonalcoholic fatty liver disease. Conclusion. Unidirectional changes in the spectrum of bile acids in nonalcoholic fatty liver disease and cholelithiasis give reason to believe that the trigger mechanism in the disturbance of bile acids metabolism is the liver. Reduction of primary bile acids, imbalance of phospholipids and cholesterol disrupt the stabilization of bile, resulting in unfavorable conditions in the bile ducts to form stones.

The aim. Find out the nature of the changes of the hepatobiliary system in patients with intestinal bacterial overgrowth and study the possible mechanisms of their association.Materials and methods. 148 patients with intestinal bacterial overgrowth and intestinal dysbiosis were examined. The level of total cholesterol, cholestasis and cytolysis markers was determined in the blood using the analyzer «Labsystems» (Finland). Intestinal bacterial overgrowth syndrome was assessed using a hydrogen breath test with lactulose on the LactophaH2 apparatus of AMA (St. Petersburg). Intestinal dysbiosis was determined by plating feces on nutrient media. Bile acids in bile were determined on the AmazonX mass spectrometer (Bruker Daltonik GmbH, Bremen, Germany). Ultrasound examination of the abdominal cavity performed with the apparatus «SHIMADZU SDN-500» (Japan). Liver elastography was performed using the AIXPLORER apparatus (France).Results. The syndrome of intestinal bacterial overgrowth in 67% of cases was established in the presence of ileocecal insufficiency, in 33% of cases — with preserved ileocecal function. The combination of intestinal bacterial overgrowth syndrome and intestinal dysbiosis was detected in 81,8% of patients. The majority of the examined patients showed clinical symptoms of damage the hepatobiliary system and intestines, which was confirmed by change laboratory parameters — increase the level of total cholesterol, markers of cholestasis and cytolysis compared with the control group. In the study of bile acids in bile, decrease free (mainlycholic) and increase conjugated (glycodesoxycholic, taurodesoxycholic, glycocholic, taurocholic) bile acids was observed compared with the control group. In general, patients with the syndrome of intestinal bacterial overgrowth revealed the presence of non-calculous cholecystitis — in 11,5% of cases, I stage of cholelithiasis — in 25,7%, II stage of cholelithiasis — in 18,9%, non-alcoholic fatty liver disease on stage steatosis and steatohepatitis — in 43,9% of cases.Conclusion. Intestinal bacterial overgrowth syndrome is the beginning of bacterial translocation, which is the triggering factor in inflammation of the liver and biliary tract. In turn, diseases of the hepatobiliary system contribute to the development of intestinal dysbiosis by reducing the synthesis of bile acids with antibacterial action, as well as violations of their excretion. Thus, strong association of intestinal bacterial overgrowth syndrome with damage to the hepatobiliary system has been established.

The review presents an analysis of the literature on the toxic effects of bile acids on the acinar cells of the pancreas as a possible pathogenetic factor in acute biliary pancreatitis. It is shown that at an early stage of acute biliary pancreatitis the damage to the acinar cells is manifested in disturbances of the secretory process, activity of the digestive enzymes, as well as in the disturbances in the structure and function of cell membranes and organelles. It is assumed that the general mechanism that mediates the final death of the acinar cells might be aberrant calcium signaling pathways induced by bile acids. Bile acids can be taken up by the acinar cells through Na+ -dependent and Na+ -independent transporters located at the plasma membrane, or by a G-protein-coupled receptor for bile acids. Cytosolic bile acids induce sustained increase in calcium concentration via mechanisms that involve depletion of intracellular Ca2+ stores and activation of Ca2+ entry. Overload with Ca2+ leads to intracellular trypsinogen activation, mitochondrial depolarization, depletion of ATP and subsequent death of the acinar cells.

Aim. The aim of the review is to present current data on the relationship between non-alcoholic fatty liver disease (NAFLD) with the metabolic disorders of bile acids (BA) and changes in the composition of the intestinal microbiota.Background. NAFLD is accompanied by a change in the intestinal microbiotic composition: the proportion of taxa deconjugating BAs increases, while the proportion of taxa converting primary BAs to secondary ones decreases. The number of bacteria forming lipopolysaccharide (LPS) also increases. LPS, entering the liver with the portal vein blood, promotes the development of its inflammation and insulin resistance. The disturbance of bile acid metabolism through the effect on the FXR and TGR5 receptors also leads to insulin resistance and liver steatosis. FXR probiotics and agonists are promising drugs for the NAFLD treatment.Conclusion. In the course of NAFLD, a change in the composition of the intestinal microbiota is observed, which contributes to the development of inflammation in the liver and disrupts the metabolism of bile acids, leading to insulin resistance.

Intrahepatic cholestasis of pregnant women (ICPW) is associated with an increased risk of complications of pregnancy. Objective prognostic markers of adverse pregnancy outcomes except for a high level of bile acids (BA) in the mother's blood serum, exceeding 40 μmol/l, do not currently exist. However, the determination of the BA levels is not available in all laboratories, which indicates the need to search for other informative prognostic markers of complications of pregnancy in patients with ICPW. Objective: to determine the risk factors for adverse pregnancy outcomes in ICPW. Materials and methods. A prospective study included 97 pregnant women diagnosed with ICPW. The diagnosis was established with an increase in the serum level of the BA in excess of 10 μmol/l. Patients underwent clinical and laboratory examinations with assessment of biochemical markers of liver damage, antioxidant status (determination of superoxide dismutase, glutathione peroxidase, selenium, zinc level). Biochemical indices and severity of pruritus were assessed at the time of diagnosis of ICPW, after 1 and 2 weeks of treatment with ursodeoxycholic acid (UDCA) at a dose of 500 mg to 2 g per day. In the study of perinatal outcomes, the term of delivery, the method of delivery, the presence of signs of intrauterine fetal hypoxia, the state of the fetus at the time of birth were taken into account. Results of the study. In the observed group of patients, the incidence of preterm birth was 31.9%, intrauterine fetal hypoxia 29.9%, pre-eclampsia 23.7%, the need for a cesarean section due to the development of pregnancy complications arose in 40 (41.2%) cases. The risk factors for complications of pregnancy in patients with ICPW were: early onset and longer duration of ICPW, reactivation of cholestasis after its regression against the background of UDCA treatment and less effective treatment of skin itching in patients with manifest forms of ICPW. The laboratory markers of adverse pregnancy outcomes were a high level of maternal total serum BA and a low efficiency of its reduction against the background of treatment, a slow rate of decrease in hepatic transaminase activity against the background of treatment, a low level of antioxidant protection enzymes. The use of sex hormones during pregnancy promoted more frequent development of preeclampsia and increased the frequency of indications for cesarean delivery. The conclusion. Patients with early manifestation of ICPW and reactivation of cholestasis after its regression on the background of treatment, low effectiveness of treatment of pruritus, and also taking drugs of sex hormones require special attention and active management in connection with an increased risk of complications of pregnancy. It is advisable to carry out dynamic monitoring of the level of BA, hepatic transaminases and antioxidant enzymes in dynamics against the backdrop of treatment with ICPW to assess the effectiveness of treatment and timely prediction of possible complications of pregnancy.

Bile acids play a leading role in the physical and colloidal properties of bile stabilization. Lack of bile acids consequences result in the formation of cholesterol stones in the gall bladder, diarrhea and steatorrhea, fat-soluble vitamins impaired absorption, and kidney stones formation (oxalates). Investigation of altered bile composition, especially the content of bile acids, in patients with gallstone disease by means of modern analytical analysis methods (liquid chromatography with mass spectrometric detection) would complement the modern ideas about mechanisms of lithogenesis and aim efforts at prevention of stone formation in the gall bladder, that was the purpose of our work. Materials and methods. Bile samples were tested for bile acid content using liquid chromatography with mass spectrometry. 14 samples of bile from patients with cholelithiasis were included in the main group, and control group consisted of 7 bile samples from practically healthy persons. Results. In patients with cholelithiasis there is an increase in the content of conjugated forms of bile acids – glycolic acid in 2 times (p = 0.002), taurocholic acid in 1.57 times (p = 0.062) compared with practically healthy persons. In patients with cholelithiasis, the ratio of taurocholic to glycolic acidі content (0.95 vs. 1.27, p = 0.0179), as well as glycogenodeoxycholic to glycodeoxycholic acid (1.11 vs. 1.58, p = 0.027) is significantly less than that in practically healthy persons. In addition, one in two patients with cholelithiasis does not reveal the presence of ursodeoxycholic acid in the bile. Conclusions. The lithogenic properties of bile are primarily caused by conjugated forms of cholic acid with glycine and taurine content violation. The ratio of taurocholic to glycolic acid content in patients with cholelithiasis is significantly lower than the similar index in practically healthy persons (0.95 vs. 1.27, p = 0.0179). The ratio of glycine conjugated bile acids content, namely glycogenodeoxycholic to glycodeoxycholic acid, in patients with cholelithiasis is also significantly lower than in practically healthy individuals (1.11 versus 1.58, p = 0.027). Ursodeoxycholic acid is not defined in bile of one in two patients with cholelithiasis (50 %), while it is absent in every seventh among practically healthy persons (14.29 %).

According to the modern concepts an intestinal microbiome has a significant effect on the functioning of the whole body including the immune system, digestive tract and liver in particular. This review displays current understanding of the intestinal microbiome impacting on the progression of chronic viral hepatitis caused by HCV- and HBV-infection, as well as changes in bowel microbiocenosis features depending on the duration of chronic process in the liver. It is indicated that chronic hepatitis to cirrhosis progression is accompanied by Bifidobacterium and strains of lactic acid (Lactobacillus, Pediococcus, Leuconostoc, Weissella) number decreasing and overgrowth of opportunistic species such as Enterococcaceae, Veillonellaceae, Enterobactericeae, Candida spp., Clostridia spp. This phenomena caused by PAMPs entry into the bloodstream including various types of toxins playing a role in liver immune inflammation processes progression. Thus patients with HBV and HCV infection are increased the number of CD4+, CD25+ in the blood and liver significantly, FOXP3+ Treg cell providing an immunosuppressive effect, and the function of specific CD8 lymphocytes is reduced and insufficient leveling virus significantly. Microbial imbalance has a negative effect on the biosynthesis of bile acids and sterolbiom functioning of our body as a result of changes in the balance between Bacteroides/Firmicutes, overgrowth of pathogenic and opportunistic Enterobacteriaceae, Veillonellaceae, Alcaligeneaceae and Porphyromonadaceae, Clostridium cluster XIVa, Helicobacter spp. and Clostridium difficile. These toxins formation and various carcinogenic metabolites from these strains leads to the inflammation development in the intestines and as a consequence to the progression of the inflammatory process in the liver. In turn, the reduction in the bacteria number producing short-chain fatty acid contributes to intestinal colonization by pathogenic representatives Gracilicutes (Salmonella, Shigella, enterohaemorrhagic E. coli) and Firmicutes (Clostridia), the toxins having a direct toxic effect on the liver. It is examined a little-studied question about a possible cofactor effect of enteric viruses (rotavirus, adenovirus, poliovirus type 1, Coxsackie virus, ECHO) and bacteria (Shigella, Salmonella, diarrheagenic E. coli, C. jejuni) on the progression of chronic hepatitis. In view of the above, it is necessary to study in further detailed the influence of the intestinal microbiome on the progression of chronic hepatitis HBV/HCV etiology in order to develop a comprehensive approach to treatment and reduce the risk of adverse outcomes in patients.

TGR5 are G-protein-linked, membrane bile acids receptors that widely express in tissues of animals and humans. Namely tissue localization of TGR5 determines biological effects of activation of these receptors. This review focuses on the role of TGR5 as a new pharmacological target for the treatment of patients with metabolic syndrome, diabetes, obesity, atherosclerosis, liver disease and cancer processes.

The aim of review. To present data on pathogenic significance of bile acids for upper regions of gastrointestinal tract (GIT) and to describe medical properties ursodeoxycholic acid (UDCA) at reflux-gastritis.Summary. Reflux-gastritis is chemical type gastritis, morphologically manifested by foveolar hyperplasia, edema, proliferation of smooth-muscle fibres of lamina propria, insignificant chronic inflammation. There is evidences of relation of intestinal metaplasia to duodenogastric reflux (DGR). Bile acids at certain conditions possess damage effect on mucosa of the stomach and all GIT. They can increase endocellular concentration of calcium which is responsible for toxic effects of bile acids as a secondary messenger. Increase of endocellular calcium stimulates secretion of pepsinogen and acid production in the stomach, that in the case of decreased cytoprotective factors by DGR can cause changes mucosal injury. According to the modern point of view bile acids are associated with a lot of neoplasms of digestive organs, including esophageal, stomach, small intestine, liver, pancreas and colorectal cancer. Exposition of bile acids results in formation of active forms of oxygen and nitrogen, damage of DNA, mutagenicity, induction of apoptosis in short-term prospect and resistance to apoptosis in long-term prospect. Gastric remnant gastritis is consideres to be a premalignant disease, thus bile acids play essential role in carcinogenesis. UDCA possesses choleretic effect and ability to displace toxic hydrophobic bile acids. It protects from oxydative stress, stabilizes cell membranes and inhibits apoptosis. At reflux-gastritis UDCA relieves clinical symptoms, improves of state of mucosa of the stomach and esophagus, and possess series of cytoprotective properties.Conclusion. Prescription of UDCA is pathogenicly proved in patients with reflux-gastritis and gastroesopha geal reflux disease (GERD) with non-acidic refluxes. Cytoprotective and antiapoptotic effects of UDCA at reflux-gastritis are especially significant from the point of view of smoothing cancerogenic potential of bile acids.

The aim of review. Nuclear receptors are ligandactivated transcription factors, involved in regulation of metabolism and transport of bile acids (BA) both under physiological, and cholestatic conditions. Accumulation of BA and other bile components in hepatocytes during cholestatic liver diseases is accompanied by liver cells damage and ready to fibrosis and cirrhosis. This article is devoted to the above-mentioned issues.Key points. Some adaptive processes including change of hepatocyte transport systems expression reduction of BA synthesis, activation of BA detoxication and elimination are upredgulated during cholestasis. All listed mechanisms are directed to minimize damage hepatocytes and nuclear receptors play the main role in their regulation. Nevertheless, realization of these adaptive processes, apparently, is insufficient to prevent cholestatic liver diseases.Conclusion. Accumulation of data on metabolism and transport of BA under physiological and cholestatic conditions allows not only to explain the mechanism of action of the drugs empericaly utilized for treatment of cholestasis for many years, but also to develop new, probably, more effective pharmaceuticals. So, it is supposed, that application of nuclear receptor ligands will help to boost hepatocyte protection mechanisms, and, hence, to slow down or arrest progression of disease.

Gallstone disease and chronic calculous cholecystitis are the most prevalent gastroenterological diseases which require a surgical treatment. The quantity of patients with, gallstone disease or chronic calculous cholecystitis constantly is increased with, raise in age. Accordingly, the quantity of patients after cholecystectomy grows. The cholesterol gallstones and. mixed, gallstones in the gallbladder can make up from 60 % up to 80 %. Now cholesterol cholecystolithiasis is considered, as a complex of metabolic disorders in a liver and. a gallbladder. The mechanism of formation of cholesterol gallstones unites set of some conditions: cholesterol supersaturation of gallbladder bile and. precipitation, of cholesterol monohydrate crystals, hypersecretion, of glycoprotein, mucins and. gallbladder hypomotility. Treatment of gallstone disease and chronic calculous cholecystitis includes the ordinary opened, cholecystectomy and. laparoscopic cholecystectomy, sometimes cholecystolithotomy. Organ preservation, methods are applied only for the treatment of cholesterol gallstones: extracorporeal shock-wave lithotripsy of gallstones, local contact chemical litholysis with. MTBE and. systemic litholysis with, bile acids (CDCA and. UDCA).

There are two sources of cholesterol: endogenous (biliary) and exogenous (dietary) in human organism. Biliary cholesterol arrives with cyctic and. hepatic bile in small intestine and. is mixed, with dietary cholesterol. The pool of absorbed cholesterol in the ileum, contains 1/3 of dietary and. 2/3 of biliary cholesterol. Cholesterol concentration, in blood serum, depends on: 1) absorption, of dietary and. biliary cholesterol in the ileum; 2) absorption, of biliary cholesterol in the gallbladder; 3) activity of biosynthesis of cholesterol in the liver and the small intestine; 4) biosynthesis of bile acids in the liver; 5) speed, of elimination, of cholesterol from blood by liver; 6) rate of excretion of biliary cholesterol with, hepatic and. cystic bile into duodenum. Together with, enterohepatic circulation, of bile acids in human organism, there is enterohepatic circulation, of biliary cholesterol. It was proposed, that regulation, of concentration, of biliary cholesterol that participates in enterohepatic circulation, can influence a level of cholesterol in blood.

The occurrence of chronic diarrhea after cholecystectomy (CCY) has been described by many researchers. However, the main mechanisms of the development of this diarrhea are not fully understood. Supposed that dysregulation of the bile acids (ВA) absorption in the ileum is played a significant role in the development of diarrhea syndrome., Aim: To determine the role of the fibroblast growth factor 19 (FGF19) level in the serum and BA concentration in feces in pathogenesis of bile acid diarrhea (ВАD) in patients after CCY., Materials and Methods: Sixty-one patients were examined at various times after CCY: 30 patients with chronic diarrhea that appeared after CCY (group 1) and 31 patients with normal stools (group 2). In all patients, the level of FGF19 in the blood serum, and the daily excretion of BA in the feces were studied. The control group consisted of 28 healthy individuals., Results: In the 1st group we found lower concentrations of FGF19 in the blood serum 86.2 ng/ml (67.8; 117.8) compared with concentrations in the 2nd group 259 ng/ml (170.6; 318.8), p0.001. The daily excretion of bile acids with feces in the 1st group was 657.4 mg/day (524.6; 830.1), which was twice more than in the 2nd group and the control group. It was established an inverse correlation between serum concentration of the FGF19 and the BA excretion in the feces in all examined patients. It indicates a possible relationship between the low concentration of FGF19 in blood serum and malabsorption of the BA., Conclusion: Low level of FGF19 in the blood serum and a high excretion of BA in the feces may be one of the causes of BAD in patients undergoing cholecystectomy. Our results indicate the important role of FGF19 in the development of chronic diarrhea, which can be considered as one of the variants of postcholecystectomy syndrome.

Bile acids were first considered carcinogenic in 1939. Since then, accumulated data have associated colon cell changes with high levels of bile acids as an important risk factor for developing colorectal cancer, which is more common among people who consume large amounts of dietary fat. Secondary bile acids formed under the influence of the intestinal microbiota can cause the formation of reactive forms of oxygen and nitrogen, disruption of the cell membrane, mitochondria, DNA damage, reduction of apoptosis, increased cell mutation, turning them into cancer cells. High-fat diet, intestinal microflora, bile acids are a risk factors for colorectal cancer.

Cancers of the gastrointestinal tract are widespread among the population and cause significant damage to the health care system. In order to improve the strategy of preventive measures and the detection of oncological diseases at the early stages, it is necessary to provide timely impact on possible risk factors contributing to the onset and progression of malignant neoplasms. This review demonstrates the association between the pathology of the biliary tract and oncological diseases of the digestive system, discusses the possible mechanisms of the influence of cholelithiasis and cholecystectomy on the development of malignant neoplasms of various parts of the gastrointestinal tract.

The article reflects current literature data on the epidemiology and risk factors of non - alcoholic fatty liver disease. An important aspect is the description of the modern views of combined lesions of the hepatobiliary tract and small intestine. Disorders of the intestinal microbiota play a special role in the development of non - alcoholic fatty liver disease. The value of enterohepatic circulation of bile acids in the development of intestinal and liver diseases was shown. It seems relevant to further study the comorbidity of the development of non - alcoholic fatty liver disease and enteropathy for the development of pathogenetically substantiated therapy.

Aim: Сomparative studying of changes in the spectrum of bile acids in bile in patients with nonalcoholic fatty liver disease and cholelithiasis., Materials and Methods: 140 patients were included in the survey: 50 - with nonalcoholic fatty liver disease and 90 - with cholelithiasis. The diagnosis of nonalcoholic fatty liver disease was established on the basis of ultrasound examination of the liver, the elasticity and fibrosis of liver by using the sonoelastography and liver biopsy. The prestone stage of cholelithiasis was established on the basis of ultrasound examination of the gallbladder and biochemical examination of bile. The level of total cholesterol, triglycerides, alanine aminotransferase, aspartate aminotransferase, total bilirubin, alkaline phosphatase and gamma glutamyl transpeptidase were studied using the analyzer "Labsystems" (Finland). The spectrum of bile acids in bile is studied by mass spectrometry on AmazonX apparatus (Bruker Daltonik GmbH, Bremen, Germany)., Results and Discussion: Biochemical blood test revealed increase of cholesterol, triglycerides, cytolysis markers, and cholestasis, the most pronounced in patients with nonalcoholic fatty liver disease. Biochemical study of bile showed increase of cholesterol, decrease the total amount of bile acids and cholatecholesterol coefficient in the vesicle and hepatic bile in patients with nonalcoholic fatty liver disease and cholelithiasis. Mass spectrometry showed decrease the total amount of free bile acids (choloidal, chenodeoxycholic, deoxycholic) and increase the content of conjugated bile acids (glycocholic, glycodesoxycholic, taurocholic, taurodeoxycholic, ursodeoxycholic), the most pronounced in patients with nonalcoholic fatty liver disease., Conclusion: Unidirectional changes in the spectrum of bile acids in nonalcoholic fatty liver disease and cholelithiasis give reason to believe that the trigger mechanism in the disturbance of bile acids metabolism is the liver. Reduction of primary bile acids, imbalance of phospholipids and cholesterol disrupt the stabilization of bile, resulting in unfavorable conditions in the bile ducts to form stones.