Summary Post- COVID syndrome refers to the long-term consequences of a new coronavirus infection COVID-19, which includes a set of symptoms that develop or persist after COVID-19. Symptoms of gastrointestinal disorders in post- COVID syndrome, due to chronic infl ammation, the consequences of organ damage, prolonged hospitalization, social isolation, and other causes, can be persistent and require a multidisciplinary approach. The presented clinical practice guidelines consider the main preventive and therapeutic and diagnostic approaches to the management of patients with gastroenterological manifestations of postCOVID syndrome. The Guidelines were approved by the 17th National Congress of Internal Medicine and the 25th Congress of Gastroenterological Scientifi c Society of Russia.

The authors consider the symbiotic microbiota of the human body as a leading factor in the health of the entire body, which should be managed in order to prevent and treat various diseases and possibilities of metabiotics and targeted metabiotics used for this purpose as the most promising direction for the treatment and prevention of diseases of various organs. It was noted that Russia is one of the first countries to assess biotechnological prospects and the importance of creating metabiotics for various purposes, capable of preventing, restoring and regulating physiological functions, biochemical and behavioral responses, signaling intra and intercellular communications, epigenetic regulation of gene expression and post-translational modification of their final products.

The authors consider diseases of internal organs as a reflection of the influence of various factors on the human exposome (as a complex symbiotic system) in the process of formation of the noosphere from the biosphere. At the same time, various exposome factors caused deep violations of the evolutionarily developed symbiotic relationships of a person with the environment and the internal environment with a violation of the basic systems of regulation and adaptation with the development of metabolic imbalance and the subsequent formation of various diseases. The important role of connective tissue in these processes, its various elements in the regulation of the structure of organs and cells, the near-cellular space, metabolism, immunity, ways of interaction with the microbiota and its network structures, decentralized forms of homeostasis regulation are considered.

The authors consider the nutriciology aspects of therapeutical problems from the perspectives of the General theory of medicine developed by them — the theory of noosphere–anthropogenic harmony. The authors consider the evolution aspects new scientifi c data on the molecular biology, microbiology and biotechnology as a part of biological culture, which determines the relationship of a person with the internal and external world and is one of the main factors in the evolution of the biosphere. The article analyzes the problems of qualitative and quantitative changes in nutrition parameters during the formation of diseases, their prevention and treatment.

The article presents the results of the analysis of clinical features of gastroenterological manifestations of a new coronavirus infection (COVID-19) caused by the pathogen SARS-CoV-2. Taking into account the stage-by-stage system assessment of the experience of treating 1,180 patients in a multi-specialty hospital transformed into an infectious hospital, the most characteristic clinical manifestations of digestive damage by SARS-CoV-2 coronavirus are described. The article focuses on verification of changes in the digestive system, both at the stage of primary examination, and during etiotropic (in combination with hydroxychloroquine and azithromycin, interferon-alpha drugs), pathogenetic (in combination with corticosteroids, heparin drugs, according to indications - an interleukin-6 inhibitor) and symptomatic (antipyretics, antiemetics and antitussive drugs) therapy, carried out in accordance with Temporary guidelines of the Ministry of health of the Russian Federation “Prevention, diagnosis and treatment of new coronavirus infection Covid-19”. Directions for the development of algorithms for clinical and laboratory, instrumental and radiological diagnostics of changes in the digestive system in patients with COVID-19 are justified.

The presented clinical practice guidelines of the Gastroenterological Scientific Society of Russia (GSSR), diagnostic, and therapeutic approaches for patients with digestive diseases during the COVID-19 pandemic. The guidelines were approved by the XXIII Congress of the GSSR and the 22nd International Slavonic-Baltic Scientifi c Forum “St. Petersburg - Gastro-2020 ON-LINE” (St. Petersburg, June 11, 2020). The presented clinical practice guidelines of the Russian Scientific Medical Society of Internal Medicine (RSMSIM) and the Gastroenterological Scientific Society of Russia (GSSR), diagnostic, and therapeutic approaches for patients with digestive diseases during the COVID-19 pandemic. The recommendations were approved at the XV National Congress of Internal Medicine, XXIII Congress of NOGR on the basis of the 1st edition, adopted at the 22nd International Slavic- Baltic Scientific Forum “St. Petersburg - Gastro-2020 ON-LINE”.

The presented clinical practice guidelines of the Gastroenterological Scientific Society of Russia (GSSR), diagnostic, and therapeutic approaches for patients with digestive diseases during the COVID-19 pandemic. The guidelines were approved by the XXIII Congress of the GSSR and the 22nd International Slavonic-Baltic Scientific Forum “St. Petersburg — Gastro-2020 ON-LINE” (St. Petersburg, June 11, 2020).

The autor sconcider the metabolic sindrom from the perspecrtive of the General theory of medicine developed by them — the theory of noospheric–anthropogenic harmoni. The paper analyzes new scientifi c data on the role of exposome, various external and internal factors that lead to the development of Metabolic syndrome. The role of various infection, disbiosis, nutrision factors (microbiota correctors, dietary fiber, etc.) are discussed.

An increasing number of gram-negative and gram-positive bacteria have been observed to secrete outer- membrane vesicles (OMVs) during their growth both under physiological and pathological conditions in vitro and in vivo. These cell-derived particles are present in many — if not all — physiological fluids. They can convey the multiple various low weight effector and signal molecules (proteins, nucleic acids, lipids, and carbohydrates) into the bacterial and host cells that have important functions in their intercellular communication and regulation. Involvement of OMVS in the various biological functions of prokariotic and eukaryotic cells make them to be key players in both physiological processes and also in pathological conditions. Additionally, the ability of OMVs to deliver molecules to recipient cell opens the possibility of their use as novel disease biomarkers and as promising drug/therapy agents. In this Review, we describe the mechanisms through which bacterial OMVs can support the host homeostasis and health and induce host pathology or immune tolerance, and discuss the possibility of these OMVs participate in innovative nanobiotechnologies.

Frequent damage to the digestive system with a new coronavirus infection, as well as its combination with gastroenterological pathology complicates the whole complex of therapeutic and diagnostic measures for such patients. Understanding the problem is complicated by a large number of conflicting scientifi c data of varying degrees of evidence. The article describes the mechanisms of gastrointestinal tract (gastrointestinal tract) aff ection by coronavirus SARSCoV-2 — induction of infl ammation and violation of the permeability of the gastrointestinal mucosa, changes in the composition and function of the intestinal microbiota, impaired intestinal-lung axis interaction. features of the clinical picture aff ecting the prognosis of the disease, explains the features of the examination, and suggests treatment methods. The article shows the features of the clinical picture that aff ect the prognosis of the disease, explains the features of the examination, suggests methods of treatment and nutritional support.

The 8-year observation data of patients with ulcerative colitis and Crohn’s disease in the North West region are presented in the article. The patients were observed in the scientific and clinical center of Military Medical academy named after S. M. Kirov, specialized in the inflammatory bowel diseases (IBD). The aim of study is to assess the gender, age and clinical characteristics of patients with inflammatory bowel diseases, epidemiological features: factors of employment and place of residence, to study the outcomes of ulcerative colitis (UC) and Crohn’s disease (CD). Materials and methods. Retrospective analysis of 485 patient’s medical charts (373 patients with ulcerative colitis and 112 patients with Crohn’s disease) in the period from 2010 to 2018 was performed. Results. The onset of inflammatory bowel diseases is most common in the age group up to 40 years. The duration of the period before the diagnosis of ulcerative colitis and Crohn’s disease averaged 2.3 years. In UC the most frequent localization of the pathological process was left-side colon (51%), in CD - terminal ileitis (29%) and ileocolitis (27%). The anemia was the most frequent complication in both form of IBD, but structuring and penetrating complications were characteristic of CD. The most of patients (80.6%) had recurrent or continuous course of IBD. Small proportion of patients (19.4%) had sustained remission throughout the follow-up period. The frequency of surgical interventions in CD (27.6%) was comparable with the registers of the European study groups of IBD. In contrast, the frequency of colectomy in UC was significantly lower (0.8%) than in the published data of European countries, due to the predominance of mild and moderate forms of UC in the observed cohort. Mortality of patients with IBD was higher than in the General population of St. Petersburg due to the contribution of mortality from complicated forms of IBD (15.7%), while the structure of other causes of death was comparable to the General population

In this review authors discuss modern condition of treatment and prophylaxis of human metabolic diseases associated with microecological imbalance of intestinal symbiotic microbiota. Now the most frequently for these aims various probiotic nutrient additives and functional fermented foods prepared on the basis of living bacteria have been used. Unfortunately such probiotics have not possessed the real effectiveness and are not completely safe. Instead of traditional commercially available living probiotics the authors suggest to use novel microecological means (metabiotics) that are structural components of probiotic bactrerial strains, and/or their metabolites and/or signaling molecules with known chemical structure. Metabiotics can optimize host‑specific physiological, regulator, metabolic and/or hormone/behavior functions and reactions. Metabiotics possess some advantages in future personalized medicine because they have exact chemical structure, well dosed, safe and long shelf‑life.

Background: Epidemiological studies performed in different countries have identified a number of trends that allow to predict the problems related to the prevalence of inflammatory bowel diseases (IBD), their severity and healthcare resources utilization. Aim: To present comparative results of two large epidemiological studies of IBD in the Russian Federation (RF), i.e. ESCApe and ESCApe-2. Materials and methods: Two multicenter cross-sectional cohort studies with a similar design were performed at three-year interval. The studies had the common aim: to identify social and demographic and clinical particulars of ulcerative colitis (UC) and Crohn’s disease (CD) in RF, as well as treatment options. Twenty (20) centers of gastroenterology from 17 RF regions participated in the ESCApe (2010–2011) and 8 centers from 7 RF regions in the ESCApe-2 study (2013–2014). Results: The ESCApe study included 1797 patients (1254 UC and 543 CD), whereas the ESCApe-2 included 1000 patients (667 UC and 333 CD). Patient demographic and social characteristics: In both studies, female: male ratio was similar in UC and CD. Patients’ age was almost identical: in UC, median age was 38 years and 40 years in ESCApe and ESCApe-2, respectively; in CD the corresponding values were 36 and 35 years. In ESCApe, the peak UC onset was at the age of 21 to 40 years, whereas in CD it was shifted towards younger age (22.5% of the patients manifested before 20 years) and the peak incidence was in three age groups (below 20 years, 21 to 30 and 31 to 40 years). A statistically significant difference between CD and UC was found only in the age group of 11 to 20 years (22.5% vs. 13.6%, respectively, p < 0.01). In ESCApe-2, median age of disease onset in UC and CD was approximately 30 years. In both studies, urban:rural ratio for UC and CD was 4:1. In ESCApe, the proportion of current smokers among CD patients was almost two-fold higher than among those with UC (15.6 and 8.8%, respectively, p < 0.001); the same trend was found in ESCApe-2 (15 and 7.3%, p < 0.001). Socioeconomic characteristics of patients in both studies were similar: 50 to 60% were at work (professional occupation and income levels were not studied); in ESCApe 30.9% of UC patients and 40.9% of CD patients had legal disability due to various reasons (including that related to UC and CD in 12,6 and 14.9%, respectively), whereas in ESCApe-2 the respective proportions were 35.7 and 51.1%. Clinical characteristics of patients: The time from the first UC symptoms to diagnosis was similar in both studies (median, 5 months in ESCApe and 4 months in ESCApe-2); in CD patients these parameters were significantly different in both studies (12 vs. 1 month). As for the severity of the disease, the UC patients in ESCApe had mild disease in 16%, moderate in 53%, and severe in 31%, whereas the respective proportions among the CD patients were 21, 44, and 35%. In ESCApe-2, there were no patients with severe disease; mild and moderate UC were diagnosed in 51.3 and 46.6% of the patients, respectively, and mild and moderate CD, in 52.3 and 47.3%. The frequency of left-side UC was similar: 38% in ESCApе and 34% in ESCApе-2. Proctitis was more frequent in the first study (33 vs. 11%, p < 0.01), and total UC was more frequent in the second study (29 vs. 55%, p < 0.02). There were no significant differences between ESCApe and ESCApe-2 in the main CD localizations: terminal ileitis was seen in 31.3 and 35.4% of the patients, respectively, ileocolitis in 33.4 and 37.8%, colitis in 25.6 and 32.1%. The upper gastrointestinal involvement In ESCApе was found 4.4%, and mixed involvement in 5.3%. In both studies, extra-intestinal manifestations were more frequent in CD, than in UC: in ESCApe, 33.1% and 23% (р < 0.05), and in ESCApe-2 in 41.7 and 29.4%, respectively (р < 0.05). Peripheral arthropathies were most frequent. Ankylosing spondylitis was found in CD only, and primary sclerosing cholangitis, only in UC. Aphthous stomatitis was significantly more prevalent in CD in both studies. There were no significant differences in all other extra-intestinal symptoms (eye and skin involvement). Treatment characteristics: Treatment options before the study entry, as well as at the study inclusion visit were analyzed. In ESCApe, the majority of the patients had not been given any treatment before the study entry (49.1% with UC and 40.5% with CD). Three years later the situation was changing: in ESCApe-2, the proportion of treatment-naïve patients was 2.5 to 3-fold lower (15.3% with UC and 14.4% with CD), which was most probably related to increasing awareness of physicians. Before the study entry, most patients (40 to 70%) had been treated with 5-aminosalicylic acid (5-ASA). Before the second study, the patients were more frequently treated with glucocorticosteroids (GCS), immunosuppressors and genetically engineered biological agents (GEBA), but with no significant differences from the first study. 5-ASA prevailed also among the agents that were administered during the inclusion visits in both studies (80 to 90% UC patients and about 70% of CD patients). Compared to ESCApe, in ESCApe-2 there was a trend towards lower rate of GCS administration in UC and CD, but the differences did not reach the significance level. It may be explained by the absence of severe IBD types in ESCApe-2. In ESCApe, immunosuppressors were rarely used (in 14.4% of the UC patients and in 26.8% of the CD patients); however, in ESCApe-2 there were administered more frequently: up to 35.9% of the UC patients and 55.1% of the CD patients (р < 0.01 for both cases). It was unknown if immunosuppressors were used as monotherapy or in combination with GCS. Three years later, the rate of GEBA administration was also higher, but this increase was significant only in CD: 28.3% in ESCApe-2 vs. 9.2% in ESCApe (р < 0.01). According to the results of ESCApe, in the UC patients steroid resistance was seen in 23% and steroid dependency in 21%, whereas in the CD patients these values were 24 and 27%, respectively. In ESCApe-2 these parameters were not assessed. Conclusion: Both studies showed a number of patterns coinciding with the world trends, such as age and gender distribution of UC and CD patients, age at manifestation, the proportion of urban to rural residents, smoking status, prevalence and types of extra-intestinal symptoms. Unlike in European countries, moderate and severe forms of UC with extensive involvement are prevalent in RF. Low prevalence of mild and limited types of IBD is to be explained by underdiagnosis. Of note is the high proportion of patients with UC and CD treated with 5-ASA, although in CD these agents have demonstrated low efficacy. The rates of immunosuppressors and GEBA administration significantly increased in the second study, most likely, due to the implementation of a system of educational measures. Nevertheless, the rate of GEBA use in IBD remains low, which is to be related to their insufficient availability. In total, steroid resistance / steroid dependency rate amount to almost half of UC and CD cases. In general, some positive changes in the patient management are obvious in the second study. However, monitoring these changes over time could only be possible if similar studies would be performed at regular intervals.

The human symbiotic microbiota produces various bio-active molecules having chemical and functional similarity to dietary nutrients and /or endogenous compounds. Various factors and agents cause the imbalance of host/microbial dialogue. Currently for conservation and restoration of human microbial community various probiotics and prebiotics are used. Unfortunately, probiotic effects are often short term or absent or uncertain; traditional probiotics may also have non-desirable side effects in the application. For these reasons, the search for microbial molecule modifiers of host/microbe axis is emerging, especially with regard to personal medicine. These compounds have been named metabiotics (M). M are structural components of known probiotic microorganisms and/or their metabolites and/or signaling molecules that can restoring shortages and disruption of the balance of mitochondrial, microbial or cellular LMW substances with increased health effectiveness. They have some advantages (certain chemical structure, well dosed, safety, long shelf-life) in optimizing host gene expression, epigenetic, energetic, metabolic, immune, informational, regulatory, transport, neuro-hormonal and/or behavioral responses associated with the symbiotic microbiota. M can act as independent means or as enriching additives in functional foods. Simple microbial molecules can also be used in constructing hybrid M containing multiple metabolites and structural components separately or in combination with herbal compounds. Special attention should be paid to the design of M with specific targets in the host. Further investigations will clarify what natural microbial or artificial (semi-synthetic, synthetic, hybolite) pan- or selective M may affect host functions, biochemical and signal processes.

Background : Epidemiological studies  performed in different countries  have identified a number  of trends  that  allow to predict  the problems  related to the  prevalence  of inflammatory  bowel  diseases  (IBD),  their  severity  and  healthcare resources utilization. Aim :  To  present   comparative   results of two large epidemiological  studies of IBD in the Russian Federation (RF), i.e. ESCApe and ESCApe-2. Materials     and     methods :     Two    multicenter cross-sectional cohort studies with a similar design were performed  at three-year interval. The studies had the common aim: to identify social and demographic and clinical particulars of ulcerative colitis (UC) and Crohn’s disease (CD) in RF, as well as treatment options. Twenty (20) centers of gastroenterology from 17 RF regions participated in the ESCApe (2010–2011) and 8 centers from 7 RF regions in the ESCApe-2 study (2013–2014). Results : The ESCApe study included 1797 patients (1254 UC and 543 CD), whereas   the   ESCApe-2  included   1000  patients (667 UC and 333 CD). Patient demographic and social characteristics : In both  studies, female: male ratio was similar in UC and CD. Patients’ age was almost identical: in UC, median  age was 38 years and 40 years in ESCApe and ESCApe-2, respectively; in CD the  corresponding  values were  36 and 35 years. In ESCApe, the peak UC onset was at the age of 21 to 40 years, whereas in CD it was shifted towards younger age (22.5% of the patients  manifested before 20 years) and the peak incidence was in three age groups (below 20 years, 21 to 30 and 31 to 40 years).  A statistically significant difference between CD and  UC was found  only in the  age group  of 11 to 20 years (22.5% vs. 13.6%, respectively, p u003c 0.01). In ESCApe-2, median age of disease onset in UC and CD was approximately 30 years. In both  studies, urban:rural ratio for UC and CD was 4:1. In ESCApe, the proportion of current  smokers among  CD patients  was almost  two-fold  higher than  among  those  with  UC (15.6  and  8.8%,  respectively, p u003c 0.001); the same trend was found in ESCApe-2 (15 and 7.3%, p u003c 0.001). Socioeconomic characteristics of patients in both studies were similar: 50 to 60% were at work (professional occupation and income levels were not studied); in ESCApe 30.9% of UC patients and 40.9% of CD patients had legal disability due  to various reasons  (including that related to UC and CD in 12,6 and 14.9%, respectively), whereas in ESCApe-2 the respective proportions  were  35.7 and  51.1%.  Clinical characteristics of patients : The time from the  first UC symptoms to diagnosis  was similar in both  studies  (median, 5 months  in ESCApe and 4 months  in ESCApe-2); in CD patients  these parameters were significantly different in both studies (12 vs. 1 month). As for the severity of the disease, the UC patients  in ESCApe had  mild disease  in 16%, moderate in 53%, and severe in 31%, whereas the respective proportions among  the  CD patients  were 21, 44, and  35%. In ESCApe-2, there were no patients  with severe disease;  mild and  moderate UC were  diagnosed  in 51.3 and  46.6% of the  patients, respectively, and mild and moderate CD, in 52.3 and 47.3%. The frequency of left-side UC was similar: 38% in ESCApе and 34% in ESCApе-2. Proctitis was more frequent in the  first study  (33 vs. 11%, p u003c 0.01), and  total UC was more frequent  in the second  study (29 vs. 55%, p u003c 0.02). There were no significant differences between ESCApe and ESCApe-2 in the main CD localizations: terminal ileitis was seen  in 31.3 and 35.4% of the  patients,  respectively,  ileocolitis in 33.4 and 37.8%, colitis in 25.6 and 32.1%. The upper gastrointestinal involvement In ESCApе was found 4.4%, and mixed involvement  in 5.3%. In both studies, extra-intestinal  manifestations were more frequent  in CD, than  in UC: in ESCApe, 33.1% and 23% (р u003c 0.05), and in ESCApe-2 in 41.7 and 29.4%, respectively   (р u003c 0.05).   Peripheral   arthropathies were  most  frequent. Ankylosing spondylitis  was found in CD only, and primary sclerosing cholangitis, only in UC. Aphthous  stomatitis  was significantly more prevalent in CD in both studies. There were no significant differences in all other extra-intestinal symptoms  (eye and skin involvement). Treatment characteristics : Treatment options before the  study entry, as well as at the  study inclusion visit were analyzed. In ESCApe, the majority of the patients  had not been given any treatment before the study entry (49.1% with UC and 40.5% with CD). Three years later  the  situation  was changing: in ESCApe-2, the  proportion of treatment-naive patients was 2.5 to 3-fold lower (15.3% with UC and 14.4% with CD), which was most probably related to increasing  awareness  of physicians. Before the study entry, most  patients  (40 to 70%) had  been treated with 5-aminosalicylic acid (5-ASA). Before the  second  study,  the  patients   were  more  frequently  treated with  glucocorticosteroids (GCS), immunosuppressors and  genetically  engineered biological agents  (GEBA),  but  with no significant differences  from the  first study. 5-ASA prevailed also  among  the  agents  that  were  administered during  the  inclusion visits in both  studies  (80 to 90% UC patients  and  about  70% of CD patients). Compared   to  ESCApe,  in  ESCApe-2  there   was a trend  towards  lower rate of GCS administration in UC and CD, but the differences did not reach the significance level. It may be explained  by the absence of severe IBD types in ESCApe-2. In ESCApe, immunosuppressors were rarely used (in 14.4% of the UC patients  and in 26.8% of the CD patients); however, in ESCApe-2 there were administered more  frequently: up to 35.9% of the  UC patients and 55.1% of the CD patients  (р u003c 0.01 for both cases). It was unknown  if immunosuppressors were used as monotherapy or in combination with GCS. Three years later, the rate of GEBA administration was also higher, but  this increase  was significant only in CD: 28.3%  in ESCApe-2 vs. 9.2% in ESCApe (р u003c 0.01). According to the results of ESCApe, in the UC patients steroid resistance was seen in 23% and steroid dependency in 21%, whereas in the CD patients these values were 24 and 27%, respectively. In ESCApe-2 these  parameters were not assessed. Conclusion :  Both studies  showed  a  number   of patterns coinciding  with  the  world  trends,  such as age and gender  distribution  of UC and CD patients, age at manifestation, the proportion of urban to rural residents, smoking status, prevalence and types of extra-intestinal  symptoms. Unlike in European countries, moderate and severe forms of UC with extensive involvement are prevalent in RF. Low prevalence  of mild and limited types of IBD is to be explained by underdiagnosis. Of note is the high proportion of patients  with UC and CD treated with 5-ASA, although in CD these  agents  have demonstrated low efficacy. The rates of immunosuppressors  and GEBA administration significantly increased  in the second  study, most likely, due to the  implementation of a  system  of educational measures. Nevertheless, the rate of GEBA use in IBD remains low, which is to be related to their insufficient availability. In total, steroid resistance / steroid dependency rate amount  to almost half of UC and CD cases. In general, some positive changes  in the patient  management are  obvious  in the  second study. However, monitoring  these  changes  over time could only be possible if similar studies would be performed at regular intervals.