[All-Russian Consensus on Diagnosis and Treatment of Celiac Disease in Children and Adults]. / Vserossiiskii konsensus po diagnostike i lecheniyu tseliakii u detei i vzroslykh.

The paper presents the All-Russian consensus on the diagnosis and treatment of celiac disease in children and adults, which has been elaborated by leading experts, such as gastroenterologists and pediatricians of Russia on the basis of the existing Russian and international guidelines. The consensus approved at the 42nd Annual Scientific Session of the Central Research Institute of Gastroenterology on Principles of Evidence-Based Medicine into Clinical Practice (March 2-3, 2016). The consensus is intended for practitioners engaged in the management and treatment of patients with celiac disease. Evidence for the main provisions of the consensus was sought in electronic databases. In making recommendations, the main source was the publications included in the Cochrane Library, EMBASE, MEDLINE, and PubMed. The search depth was 10 years. Recommendations in the preliminary version were reviewed by independent experts. Voting was done by the Delphic polling system.

[TROPHOLOGY ASPECTS OF NOOCPHEROGENESIS. On the 90th anniversary of A M Ugolev].

This paper presents an analytical review of A. Ugolev's scientific heritage (the theory of adequate nutrition, all-purpose functional blocks, the unity of natural and artificial technologies, the discovery of membrane digestion, new doctrine--trophology) to explain trophological aspects of noospherogenesis. The authors have presented their specific views for the development of these ideas; the theory of therapeutic infections, the holistic theory of nutrition, the endoecological deficiency syndrome, the activation of all-purpose functional blocks, evasion receptors, new principles of treatment with the effects on microbiota, combining the essence of the diseases and their treatment.

NUTRITIONAL FACTORS OF ANEMIA IN ULCERATIVE COLITIS PATIENTS.

The study aim was to assess the relationship between nutritional markers decrease and hemoglobin level in ulcerative colitis (UC) patients. METHODS: The cross-sectional retrospective analysis was performed. Data from medical records of 103 ulcerative colitis patients was included to analysis. Demographic characteristics, disease behavior, gut involvement extension, hemoglobin and total serum protein levels were collected. Body mass index (BMi) and fat-free mass index mass were collected retrospec- tively from bloimpedance analysis data. A multiple linear regression analysis was performed to study the relationship be- tween nutrition status parameters and hemoglobin level adjusted for demographic and diseaseTassociated characteristics. RESULTS: Prevalence of anemia in the sample was 37.9%. In adjusted multiple linear regression model total serum protein level and fat-free mass index were directly associated with the hemoglobin level: standardized ß 0.369 (p = 0.010) and standardized ß = 0.509 (p <0.001) respectively. CONCLUSIONS: We assume undernutrition is one of causative agents of anemia in UC patients. It is likely the anemia treat- ment in UC patient with undernutrition must be performed with nutritional support.

METABOLIC DYSBIOSIS OF THE GUT MICROBIOTA AND ITS BIOMARKERS.

Existing methods of clustering of gut microbiota (enterotypes, clusters, gradients), as well as the term 'phylogenetic core' do not reflect its functional activity. The authors propose to describe the key microbiora using term 'phylometabolic core of intestinal microbioca which more accurately reflects the functional importance of metabolically active microbiota. Phylometabolic core includes functional groups of microorganisms that perform similar metabolic functions: butyrate-producing bacteria, propionate-producing bacteria, acetate-produc- ing bacteria (acerogens), hydrogenosrophic microorganisms (reductive acetogens, sulfate-reducing bacteria, methanogens), lactate-producing and lactate-utilizing bacteria, bacteria involved in bile acids metabolism, bacteria that metabolize proteins and amino acids, vitamin-producing microorganisms, oxalate-degrading bacteria and others. The hypothesis that disturbance of microbial metabolism is the root of many human diseases is discussed. The microbial dysmexabo- lism leads to the metabolic dysbiosis (a particular form of dysbiosis) that is primarily characterized by metabolic abnormalities (e.g. serum, urinary, fetal or exhaled air). Metabolic dysbiosis is not necessarily accompanied by appreciable quantitative and/or qualitative changes in microbiora composition that called taxonomic dysbiosis. Since in the metabolic dysbiosis metabolic pathways can be switched only, it means the need for completely different approaches to its assessment using metabolomics (metabolic fingerprinting, metabolic profiling, meta-metabolomics). Metabolites concentrations in colon (feces, biopsy samples), blood (serum, plasma), urine or exhaled air, as well as metabolic profiles of examined substrates can serve as biomarkers. The main clinical variants of metabolic dysbiosis are due to the disturbances in microbial synthesis of short-chain fatty acids (primarily butyrate and propionate) and due to increasing bacterial production of hydrogen sulfide, ammonia and secondary bile acids (particularly deoxycholic acid). These kinds of metabolic dysbiosis can eventually lead to inflammatory bowel disease (IBD) or colorectal cancer (CRC). The metabolic dysbiosis due to bacterial choline dysmetabolism followed by overproduction of trimethylamine (TMA), arherogenic precursor of trimethylamine N-oxide (TMAO), is associated with atherogenesis and increased risk of cardiovascular disease. Dysmetabolism of aromatic amino acids leads to changes in the microbial production of phenylalanine and tyrosine derivatives (phenyl carboxylic acid, p-cresol) and tryptophan indole derivatives (indole carboxylic acid, indole) and contributes to pathogenesis in lBS. IBD, CRC, chronic liver and kidney diseases, cardiovascular diseases, autism and schizophrenia. Metabiotics, a new class of therapeutic agents, e.g. based on microbial metabolites, can correct metabolic dysbiosis, prevent diet- and microbiota-relared diseases and increase the effectiveness of treatment.

FUNCTIONAL FOODS ARE CRITICAL COMPONENTS OF TREATMENT OF METABOLIC DISORDERS IN CELIAC DISEASE.

AIM: To evaluate the effectiveness of Native-complex functional food to correct nutritional disorders and to normalize gastrointestinal motor activity in celiac disease (CD). METHODS: 20 CD patients with constipation and metabolic disorders were included in the study (age 31.8?9.5 years, male to female ratio 1:5.3). The diagnosis of CD was confirmed by clinical and anamnestic data, endoscopy, histopathology of duodenal biopsy specimens, HLA-DQ2 and HLA-DQS typing. All patients received Native-complex Fucus jelly (Kelp jelly) within 2 months. RESULTS: At the beginning of the study45% of patients had stools corresponding to the Bristol Stool Form ScaleType 1,40% of patients had Type 2 stools and 15% of patient had Type 3 stools. 15 patients (75%) showed a decrease in fat mass and 13 patients (65%) showed a decrease in fat-free mass indicated by bloimpedance measurement. All patients had low values of total bacterial counts and increased abundance of pathobionts including fungi and viruses in fecal microbiota. Supple- mentary nutrition significantly improved symptoms, intestinal circadian rhythms and stool consistency in CD patients. At the end of the study 70% of patients had daily bowel movements, 30% of patients had stools every other day. The average stool frequency was 5,95 ? 1,80 per week. 80% of patients had Type 4 or Type 5 stools,20% of patients had Type 3 stools according to the Bristol Scale. Supplementary nutrition significantly improved gut microbiota profile. CONCLUSION: Long-term gluten-free diet in celiac disease leads to a decrease in dietary fiber and polysaccharides consumption and promotes intestinal dysbiosis. Functional foods improve symptoms; stool consistency and gut microbiota profile in adult celiac patients on gluten-free diet.

THE PSYCHO-PHYSIOLOGICAL STATUS IN CELIAC DISEASE.

Based on the results of a comprehensive study of 35 people aged from 19 to 52 years, among them 20 women and 15 men with celiac disease features of their physiological status were studied, reflecting the severity of the disease and quality of life. The diagnosis was based on the clinical and anamnestic data, endoscopy, histomorphological, immunological and genetic exams. Psychophysiological analysis showed that in celiac disease is characterized by the formation reactions with anxiety, anxiety-phobic, neurotic, affective, and hypochondriacal symptoms. The results of the study emphasized the importance of adaptive physiological capacity of the body to build tolerance to the development of psycho-vegetative, hypochondriacaldepressive and other disorders.

[NONALCOHOLIC FATTY LIVER DISEASE: DIAGNOSTIC, SYMPTOMS, TREATMENT. GUIDELINES WERE APPROVED BY THE XV GASTROENTEROLOGICAL SCIENTIFIC SOCIETY OF RUSSIA IN 2015].

According to the World Health Organization, it is recorded steady growth of the number of chronic liver diseases, including nonalcoholic fatty liver disease (NAFLD), in recent years. As an independent nosological entity, NAFLD is one of the risk factors for cardiovascular diseases, associated with abdominal-visceral obesity, peripheral insulin resistance (IR), and is regarded as the hepatic component of Metabolic syndrome (MS). Nowadays there are no generally accepted national standards for diagnosis and treatment of NAFLD for physicians, gen- eral practitioners, gastroenterologists in Russia. This was the essential reason in their development. The main reason of The guidelines development is the absence of generally accepted national standards for diagnosis and treatment of NAFLD for physicians, general practitioners, gastroenterologists in Russia. These guidelines are based on the global and local data of treatment experience of NAFLD, recently published in reviews, analytical studies in the literature. Guidelines are intended for physicians, general practitioners, gastroenterologists and contain the description of the preferred approaches to the provision of diagnostic, curative and preventive care of patients NAFLD. The quality of recommendations was grading according to the GRADE approach.

[AUTOIMMUNE LIVER DISEASES: CLINICAL FEATURES, DIAGNOSIS, TREATMENT. GUIDELINES WERE APPROVED BY THE XV GASTROENTEROLOGICAL SCIENTIFIC SOCIETY OF RUSSIA IN 2015].

The group of liver autoimmune diseases (LAD) includes autoimmune hepatitis (AIH), Primary biliary cirrhosis (PBC) and Primary sclerosing cholangitis (PSC) The guidelines on clinical diagnosis and management of patients based on a review and analysis of recent publications on this topic in the global and domestic literature and on the authors'experience in treating patients with autoimmune liver disease.

[Paradigm of dysbiosis in the modern gastroenterology. The role of microbiota in the treatment and prevention of diseases in the XXI century].

Endogenic microflora (microbiota) is one of the determinative factors of the human health. In the article new doctrine is proposed and 11 principles of microbiota's structural and functional organization are developed.

[Characteristics of the gastrointestinal myoelectrical activity in patients with nonalcoholic fatty liver disease associated with metabolic syndrome].

PURPOSE: Electrogastroenterography (EGEG) is a method of measuring action potentials of the digestive tract. The aim of the study was to evaluate the main features of the gastrointestinal myoelectrical activity (GI MEA) in patients with nonalcoholic fatty liver disease (NAFLD) associated with metabolic syndrome (MS). MATERIALS AND METHODS: GI motility function in fasting and postprandial periods by the peripheral EGEG (EGEG system "Gastroenterological GEM-01") were recorded in 33 patients with NAFLD associated with MS, 26 patients with mixed type of Irritable Bowel Syndrome (IBS) and 10 healthy volunteers aged from 18 to 70 years. RESULTS: Total fasting GI MEA data of patients with NAFLD associated with MS (Me = 40,99 MB) dominated over the same in patients with IBS (Me = 23.84 mV) and healthy volunteers (Me = 11.26 mV), the differences between EGEG parameters was not significant but critical (H = 5.997, p = 0.050). This trend was observed in postprandial period (H = 0.891, p = 0.640). In postprandial period total GI MEA in patients with NAFLD associated with MS was increased in 36.4% patients (95% CI: 24.7-56.3%) only while in IBS patients and healthy volunteers total GI MEA tract were increased in 76.9% patients (95% CI: 58.0-89.0%) and in 90.0% (95% CI: 59.6-98.2%) correspondently (χ2 = 14.12, p = 0.001). Postprandial ratio (PPR) (ratio between total GI MEA in postprandial and fasting periods) of GI MEA were less than 1.0 in patients with NAFLD associated with MS (Me = 0.65) and less then PPRs in patients with IBS and healthy volunteers (H = 10.378, p = 0.006). PPR in patients with IBS was less then this ratio in healthy volunteers (Me = 1.48 vs Me = 1.66) CONCLUSION: The increased total GI MEA is observed in patients with NAFLD associated with MS. Patients with NAFLD associated with MS have abnormal GI MEA in response on food stimulation. This fact may be important in the development of NAFLD and MS.

[On the possibilities of correction of changes of the gastrointestinal tract microbiota in patients with lung cancer treated receiving chemotherapy].

UNLABELLED: The aim of the study was the improvement of technologies of treatment of patients with the lung cancer receiving chemotherapy on the basis of using with the complex therapy of the combined probiotic based on the Bacillus subtilis strain. MATERIALS AND METHODS: 30 patients with the lung cancer receiving the first and second line of the first cycle of chemotherapy were included. The age of patients varied from 49 to 73 years, the average duration of the disease was 1 year. Patients of the main group (n = 21) received the combined probiotic based on the Bacillus subtilis strain together with the chemotherapy course. Patients of control group (n = 9) received only chemotherapeutic preparations. All patients were observed before and after treatment: the standardized inquiry for detection of intestinal complaints, microbiological research of feces (definition of qualitative and quantitative characteristics of gut microbiota), the research of metabolites of intestinal microorganisms in blood by the method of the gas-liquid chromatography - mass-spectrometry by G. A. Osipov's method. The efficiency of probiotic therapy was evaluated by results of studied indicators dynamics. RESULTS: Main symptoms of the intestinal dyspepsia were observed in patients with the lung cancer receiving chemotherapy such as constipation and intestinal microflora violations (decreased quantity of Lactobacillus, Bifidobacterium, Bacteroides and increased quantity of different pathogenic microorganisms). It was noted decreased rate of intestinal dyspepsia symptoms and improvement of intestinal microflora composition after the treatment course by the combined probiotic based on the Bacillus subtilis strain. CONCLUSION: Using of probiotic medicines with the chemotherapy in lung cancer patients is promising to reduce the frequency of gastrointestinal complaints and prevent deterioration of the gut microflora.

[Efficiency of ursodeoxycholic acid therapy in non-alcoholic fatty liver disease associated with metabolic syndrome].

INTRODUCTION: Nonalcoholic Fatty Liver Disease (NAFLD) is one of the most common liver disease. Its prevalence is 20-30% in the population of developed countries, its prevalence is 26% in Russia. NAFLD is observed in many patients with Metabolic Syndrome. Because of the wide prevalence of this disease it is required to find best drugs influencing mechanisms of its development, chronicity and progression. MATERIALS AND METHODS: 36 patients were included to the study. Mean age of patients was 43 +/- 3.9 years. Patients of the main group received the ursodeoxycholic acid within 2 months. Patients of the control group received the plant origin hepatoprotective medicine. All patients before and after treatment were carried out the biochemical analysis of blood, the liver ultrasound examination, the bioimpedance body composition analysis, the microbiological examination of faeces, the examination of metabolites of microorganisms in the blood by the method of gas-liquid chromatography - mass spectrometry, developed by Osipov G. A. RESULTS: The reduction of hepatic transaminases, the trend to normalization of the lipid profile, the reduction of body weight, the reduction of amount of adipose tissue in the body, the increase of Bifidobacterium spp., Lactobacillus spp., Enterococcus spp., the increase of levels of Bifidobacterium spp., Lactobacillus spp. Metabolites, the decrease of endotoxin plasma level and the decrease of total microbial load were observed after the UDCA treatment. The results of the study showed the prospectivity of the using of UDCA for NAFLD associated with Metabolic Syndrome.

[Serum metabolome by gas chromatography-mass spectrometry (GC-MS) in patients with ulcerative colitis and celiac disease].

Metabolomics is the emerging science of measurement and analysis of metabolome--the complete set of low molecular weight compounds in a cell, tissue, organ or whole organism. One of the aims of metabolomics is to research the response of an organism to a pathophysiological insult by measuring the concentrations of small molecule metabolites in biofluids and tissues and its dynamics. Intestinal microbiota is most probably involved in the development and maintenance of autoimmune inflammation in ulcerative colitis and celiac disease. Gas chromatography-mass spectrometry (GC - MS) of serum generates comprehensive metabolic profiles, reflecting integrated human (systemic) and gut microbial metabolism which may be altered in disease states. The aim of this study was to investigate GC - MS-based serum metabolomic profiles in UC and CD patients. Serum metabolic profiles were collected from 75 individuals: 20 patients with mild-moderate active UC, 35 CD patients, and 20 healthy controls (HC). We characterized 84 serum metabolites by use GC-MS. 18 metabolites at least have a combined (human + microbial) origin. In serum of UC patients, phenylacetic acid (PAA), 4-hydroxyphenylacetic acid (4-HPAA), 3-indolylacetic acid (IAA), succinic acid (SA) and fumaric acid (FA) were the metabolites most prominently increased, whereas 3-phenylpropionic acid (PPA) was significantly decreased. Serum of CD patients showed significant increases in IAA, 3-indolepropionic acid (IPA), SA and FA. Increased serum levels of succinic acid suggest its possible damaging effect on intestinal mucosa especially in ulcerative colitis. Orally administered butyrate + inulin as supplement to mesalazine in UC or gluten free diet in CD was effective in reducing disease activity with a marked improvement of serum metabolomic profiles (including SA reduction) and gut microbiota in both diseases. There were no any adverse events.

[Principles of development and prophylaxis of diseases in the course of noospherogenesis from the standpoint of predictive-preventive personified medicine].

Human population actively forms noosphere from the biosphere which leads to a change in biological nature of man and the range of diseases that affect him. The use of molecular predictors derived from genome, metabolome, proteome, and microbiome in clinical practice opens up an opportunity to pass to more effective predictive--protective personified medicine.

[Results of a multicenter trial "Epidemiology of Gastroesophageal Reflux Disease in Russia" (MEGRE)].

AIM: To assess prevalence of gastroesophageal reflux disease (GERD) in Russia in MEGRE trial in 6 cities of the Russian Federatiion (Kazan, Kemerovo, Krasnoyarsk, Ryazan, St-Petersburg, Saransk). MATERIAL AND METHODS: Mayo Clinic questionnaire (USA) adapted for Russia was used to question 7812 people over 18 years of age from of random population sample. The symptoms (heartburn and regurgitation) were classified as frequent if they arose once a week and more often for the last 12 months, rare symptoms arose less often than once a week. The responders with frequent heartburn and/or regurgitation were regarded as persons with epidemiological quantitative criteria of GERD. RESULTS: Heartburn occurred in 47.5% responders: frequent in 9%, rare in 38.5%. Regurgitation occurred in 42.9%: frequent in 7.6%, rare in 35.3%. GERD prevalence was 13.3% (city range 11.3-14.3%). Frequent GERD symptoms are associated with frequent gaseous eructation (24.3%), chronic cough (22.9%), chest pain (15.1%), dysphonia (11.4%.). To stop heartburn, 88% responders took antacids, 32%--blockers of histamine H2-receptors and only 23%--inhibitors of proton pump. Only 52.8% responders with frequent chest pain and 29.3% those with frequent heartburn visited a doctor. CONCLUSION: The population-based trial MEGRE conducted by international methodology in 6 cities of Russia demonstrated that GERD prevalence is 13.3%. Most of the patients pay little attention to the symptoms, do not seek medical advice and, therefore, receive no adequate treatment.

[Use of Saccharomyces boulardii in treating patients inflammatory bowel diseases (clinical trial)].

The aim of the clinical research was to study the efficacy of Saccharomyces boulardii in treatment of patients with Inflammatory Bowel Diseases. Results of investigation demonstrate more rapid regression of intestinal dyspepsia symptoms, decreasing clinical activity of IBD and improvement of intestinal microbiota composition in IBD patients have been treated by Saccharomyces boulardii. Lyophilized Saccharomyces boulardii are compatible with medical agents of the standard IBD therapy and have high level of safety.

[Functional food and psycho-intellectual abilities of man: the point of contact].

According to the 1996 WHO Report, the world is heading for a major crisis in public health as outbreaks of new and re-emerging infectious diseases are striking at increasing frequencies within the past 10 to 15 years. The given information is true not only for an infection. On the other side eventually a food of the persons considerably changes. The urgent question which needs to be addressed is the nutrition modification and optimization for public health improvement.