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Objective. To conduct a systematic analysis of data on the results of studies published in scientific journals on the pro-carcinogenic and anticarcinogenic role of microbiota, as well as on the therapeutic potential of microorganisms in oncogenesis.Material and Methods. The articles were searched using the Web of Science, Scopus, PubMed, Medline, and eLIBRARY databases. More than 150 sources dedicated to the study of the carcinogenic function of the microbiota and the possible influence of its species and quantitative composition on the efficacy and toxicity of antitumor therapy were found. Data from 71 articles were included in the review.Results. The relationship between the gut microbiota and cancer is multifactorial and bilateral: pro-carcinogenic on the one hand and anti-carcinogenic on the other hand. Microorganisms can induce tumor growth and cancer development through DNA damage and induction of mutagenesis, trigger oncogenic signals, disruption of barrier function, as well as immune response system disruption. Depletion of microbiota, the development of dysbiosis and induction of chronic inflammatory state are negative factors in the development of cancer. The anticancer effect of microorganisms is presumably based on the production of tumor-suppressive metabolites that function through multiple immune reactions. Maintenance of barrier function, competitive exclusion of pathogenic bacteria, and direct action on immune cells to prevent inflammation are also important protective factors. The presence of intratumor microorganisms in various tumors has been noted. Changes in species and quantitative composition of cancer patients’ microbiota are influenced by diet, taking antibacterial drugs, chemo-, immuno- and radiation therapy. In turn, the microbiota can affect the ongoing treatment. Numerous studies on the influence of the gut microbiota on the efficacy of immunotherapy, particularly in disseminated melanoma, have been conducted. It has been suggested that primary resistance to immunotherapy may be related to the abnormal composition of the gut microbiota. The level of gut microfora composition diversity and the number of Faecalibacterium or Bacteroidales in the fecal microbiota have been suggested to be the predictor of response to anti-PD-1 therapy. To change the composition and activity of the gut microbiota, several therapeutic methods, such as the administration of prebiotics, probiotics, synbiotics, postbiotics, fecal microbiota transplantation, as well as the change in the microbiota composition through a specific diet, are available.

Clostridium difficile was reclassified in 2016 under a new name of Clostridioides difficile. In 2021 to 2022, some changes were implemented into the main clinical guidelines on the diagnosis and treatment of infections caused by this pathogen. A two-step algorithm based on identification of C. difficile and then its toxins is still recommended for the diagnosis. The treatment regimens for the first episode and relapses of C. difficile-associated infection are based on metronidazole, vancomycin and fidaxomycin. Additional effectiveness of therapy has been associated with the use of microbiocenosis-oriented technologies aimed at restoration of the colon microbiota. In the Russian Federation, all widely applied diagnostic methods are available and all recommended antimicrobials, except fidaxomycin, as well as bezlotoxumab and fecal microbiota transplantation.

This paper provides a review of the largest studies (over the period of 2017 to 2022) on the use of fecal microbiota transplantation (FMT) for the treatment of patients with recurrent Clostridioides difficileassociated diarrhea (CDAD), including pseudomembranous colitis. A focus was made on methods of preparation and administration of fecal microbiota product. The recent systematic reviews and metaanalyses consistently consider TFM as an effective treatment option for recurrent CDAD. The different methods of fecal microbiota preparation and administration (fresh, frozen, lyophilized) show similar efficacy but differ by convenience of use.

The gut microbiome is a variable system that not only adapts to signals and information coming from humans, but also affects its host due to a complex system of interactions of living microorganisms, phages, viruses, plasmids, mobile genetic elements, molecules synthesized by microorganisms, including their structural elements (nucleic acids, proteins, lipids, polysaccharides), metabolites (signaling molecules, toxins, organic and inorganic molecules) and molecules synthesized by the human body. Modification or modulation of the microbiome by correcting the diet, the intensity of physical activity, the appointment of components of personalized products (prebiotics, probiotics, paraprobiotics, postbiotics, autoprobiotics) can lead to changes in species diversity, the metabolic profile of the intestinal microbiome and the regulation of metabolic processes, local and systemic response to infectious diseases, drug metabolism, the activity of many organs and systems due to the presence of physiological axes “gut microbiome–central nervous system”, “gut microbiome–liver”, “gut microbiome–kidneys” and some others. New, targeted directions of modification of the intestinal microbiome are being studied, which consist in targeted exposure to pathogenic microorganisms, including intracellular and resistant to antibacterial drugs.The dynamic nature of the intestinal microbiome, the ability to change and adapt under the influence of some of the studied factors opens up new promising areas of medical prevention and treatment of somatic and mental diseases. Undoubtedly, the modification of the microbiome for clinical purposes is aimed at improving human health. However, individual, not always predictable, changes in the microbiome in response to modifying factors may be due to the uniqueness of the species composition and functional potential of microorganisms in each person.

Due to the high morbidity and mortality, the problem of severe alcoholic hepatitis has not lost its relevance to date. In the absence of specific therapy, the associated to him one-month survival rate is low, and mortality rates reach 30-50 %. Although the use of corticosteroids is a scientifically proven first-line treatment for severe alcoholic hepatitis, a short-term response is observed in approximately 60 % of patients with no long-term survival benefits compared to placebo. It should also take into account the occurrence of adverse side reactions to their use in about 50 % of patients, as well as the risk of complications, in particular, bacterial and fungal infections. The second-line drugs, for example, pentoxifylline, etanercept, infliximab, N-acetylcysteine, etc. in severe alcoholic hepatitis did not show an improvement in the clinical outcome. The modern guidelines discuss the feasibility of liver transplantation in carefully selected patients who do not respond to corticosteroid treatment with severe alcoholic hepatitis. Nevertheless, due to numerous contradictions, it is too early to talk about the introduction of this approach into clinical practice. In recent years, some progress has been made in understanding the pathophysiological mechanisms of the development of alcoholic hepatitis, which served as an impetus for new directions of its pathogenetic therapy. One of them is the techniques that provide intestinal eubiosis, in particular, through the fecal microbiota transplantation. The purpose of the review was to describe the pathophysiological prerequisites and therapeutic potential of fecal microbiota transplantation from healthy donors to patients with severe alcoholic hepatitis. Experimental studies have shown a positive effect of fecal microbiota transplantation on the intestinal microflora, which led to a weakening of alcohol-induced liver damage. In patients with severe alcoholic hepatitis, it improved the severity of its symptoms and contributed to increased survival compared to those receiving corticosteroids. These preliminary results are encouraging and create conditions for further clinical trials involving a large cohort of patients with severe alcoholic hepatitis, which will allow us to identify those for whom fecal microbiota transplantation will be most effective with minimal risk of complications.

Obesity and associated metabolic diseases are often accompanied by changes in the gut microbiota leading to metagenome gene diversity decrease. Fecal microbiota transplantation (FMT) is one of the most effective methods for correcting the intestinal microflora. FMT obtained from healthy donors has been proven to be an effective treatment of infections caused by Clostridium difficile. The use of FMT for correction of metabolic disorders is promising, however, data on its application is limited and has contradictory results. In our work, two patients (siblings) presented with obesity grade II and various types of diabetes mellitus (DM): the older brother (44 years old) with diabetes mellitus type 2 (DM 2), a younger brother (39 years old) with diabetes mellitus type 1 (DM 1). Both patients underwent FMT as part of complex antidiabetic therapy. During the course of treatment, a decrease in body weight was noted in both patients (4–5 kg for the first month of observation, then -1–2 kg per month). One year after FMT, a patient with type 2 diabetes showed a decrease in the severity of insulin resistance (IR), measured by the hyperinsulinemic euglycemic clamp test (initial M-index 2.42 mg/kg*min, after 1 year — 3.83 mg/kg* min) as well as the maintenance of satisfactory carbohydrate metabolism compensation against the diminishing the hypoglycemic therapy. In a patient with DM 1, no significant dynamics of carbohydrate exchange indices, including detected glycated hemoglobin (HbA1c), insulin dose and IR were during the observation period. Metagenomic sequencing of stool samples (n = 20) collected from both patients before and within 1 year after FMT showed no significant changes in the taxonomic profile of the microbiota at the level of microbial families. Metabolomic analysis of the composition of feces showed no directed changes in the composition of metabolites after the FMT procedure, the nature of changes within the samples from each patient during the entire study period was random. Thus, FMT had no effect on the course of DM1, but served as a starting point for weight loss and improvement glucose profile in DM2. However, convincing data confirming a causal correlation between FMT and improvement in the course of T2DM have not been obtained.

Introduction and purpose: While irritable bowel syndrome (IBS) and functional dyspepsia (FD) are common problems in everyday clinical practice, their treatment often remains inefficient. The aim of our work is to present the newest discoveries and research conducted in the topic, while putting special accents on methods available in Poland. We decided to refer to British Society of Gastroenterology guidelines of treatment of IBS and FD as commonly accepted treatment standards in Europe. Description of the state of knowledge: Number of patients suffering from IBS and FD remains high. According to current research, there are some new therapeutical options in IBS: fecal microbiota transplant, spinal catepsin S, olorinab and tenapanor. Methods already being in use in other applications such as vitamin D supplementation, losartan and fecal microbiota transplant are also being investigated. Fecal microbiota transplant seems the most promising one. There are no new treatment options in FD, however there are new research on already used rifaximin and prokinetics, which show their efficacy. Intensive research is being conducted on the use of herbal medicines in treatment of FD. Even though some papers prove the effectiveness of acupuncture we have decided to omit this topic due to its controversial nature. Conclusions: Treatment of IBS and FD remains difficult, there are few advances in that area. Unconventional methods such as herbal medicine and fecal microbiota transplant seem to be gaining in importance.

Alcohol-related liver diseases are one of the leading causes of death worldwide, primarily due to complications of liver cirrhosis (LC). Early detection of alcohol-induced liver fibrosis (LF) is a difficult task, since often alcoholic liver disease (ALD) is clinically manifested only at late stages. Given that not all alcoholic suffer from ALD, the widespread use of liver biopsy to verify the diagnosis is not advisable. Despite the variety of proposed non-invasive methods for assessing the severity of LF in patients with ALD, none of them has sufficient validation and therefore cannot be recommended for widespread use in clinical practice. The most well-studied transient elastography, due to its suboptimal specificity, can be effectively used only to exclude clinically significant LF or LC. The only proven approach to treat ALD is persistent and total alcohol abstinence. While the therapeutic options for patients with severe forms of acute hepatitis remain unchanged since the 70s of the last century and are based mainly on the use of corticosteroids, currently, there are no approaches to antifibrotic therapy of ALD approved by the guidelines. At the same time, modern achievements in understanding the pathophysiological mechanisms of this disease have served as an impetus for the development of ways to solve the problem. In particular, providing intestinal eubiosis may be an important goal for the prevention and treatment of alcohol-induced LF. Randomized controlled multicenter trials involving a large number of patients are needed to confirm this and other hypotheses related to antifibrotic therapy of ALD and to accept them as a standard of medical care.

Introduction The World Health Organization (WHO) recognizes obesity as one of the ten most important threats affecting human health. The occurrence of obesity has been found to be closely linked to the phenomenon of intestinal dysbiosis. Fecal microbiota transplantation (FMT) can be an effective method of modifying and normalizing the composition of the intestinal microbiota. It involves the insertion of stool from a healthy donor into the recipient's digestive tract. Studies have found that FMT is effective in a wide range of diseases, but the evidence for its use in obesity treatment is limited. Aim of the study The purpose of the study was to examine the efficacy of fecal microbiota transplantation in the treatment of obesity. Materials and methods A search was conducted using PubMed database. Articles were searched in English using the following key words: fecal microbiota transplantation, gut microbiota, obesity. Results FMT from lean donors had no effect on weight loss in obese individuals. However, the procedure may help reduce abdominal obesity, especially in women. Studies present mixed results in terms of changes in insulin sensitivity, but most of them demonstrate the lack of effect on it. Metabolic parameters, resting energy expenditure, caloric intake and obesity markers remained unchanged. Lower HbA1c levels were observed in patients at week 6 after FMT, although this effect was temporary. Patients' quality of life after FMT did not change. No major side effects have been reported. Conclusion The findings suggest that fecal microbiota transplantation from lean donors does not contribute to weight loss in obese patients. Although FMT is ineffective for treating obesity, it can reduce visceral fat, particularly in women.

Obesity and type 2 diabetes mellitus (T2D) are two non-infectious pandemics of the XXI century. Despite a large number of studies devoted to the development of obesity and T2D, it seems complicated to overcome the ongoing growth in the number of cases. In these situations it is necessary to investigate new approaches for the prevention and treatment of such diseases. One of these approaches is to study the role of gut microbiota in the disturbance of carbohydrate and lipid metabolism. This manuscript describes the role of the microbiota in obesity and T2D. The aim of the review was to describe various approaches to change the composition of the gut microbiota and to determine its impact on metabolic risks. To assess the relationship between T2D development and changes of microbiota composition we considered a number of studies devoted to the consequence of these pathophysiologic mechanisms in various situations: the effect of drug treatment, bariatric surgery and microbiota transplantation. Possible metabolically protective gut microbiota composition is discussed.

The article presents current data on the role of gut microbiota in the development of urinary tract infections. The main pathogenetic mechanisms contributing to the chronic recurrent course of the disease, the spread of antimicrobial resistance, as well as their connection to the disorders of gut microbiota are shown. It is known that most pathogens of urinary infections originate from the gut microbiota, where they exist for a long time, forming reservoirs. The normal composition and functions of the microbiota prevent colonization of the intestine by pathogenic bacteria and reduce the risk of developing this disease. Ways of correction through diet, probiotics, as well as fecal microbiota transplantation are considered. Modulation of gut microbiota may be a promising approach in the treatment and prevention of urinary tract infections. Meanwhile, a qualitative evidence base on the effectiveness of this strategy has not been formed. Further research in this direction is required.

The article presents modern data on the formation, structure, functions and possibilities of correction of the gut microbiota. The gut microbiota is a collection of living organisms that inhabit the human intestine and form a complex microecological system that performs many functions. It is known that the composition and state of the gut microbiota is influenced by both environmental factors, such as diet and lifestyle, and the human body, including genetic predisposition. A violation in this system (dysbiosis) can provoke the development of a number of diseases and pathological conditions, in which the correction of the gut microbiota may be a promising therapeutic strategy. The most common methods of correcting dysbiosis are dieting, the use of pro-and prebiotics, and fecal microbiota transplantation. The diet affects the qualitative and quantitative composition and functions of the gut microbiota, the activity of its individual representatives. Probiotics are used to modulate, preserve the gut microbiota in dysbiosis, as well as to prevent its development. Fecal microbiota transplantation is performed by transferring the microbiota from a healthy donor. This method is one of the most effective ways to treat Clostridium difficile infection. This review article also presents the results of fecal microbiota transplantation in patients with inflammatory bowel disease and hepatic encephalopathy. It is shown that after transplantation, there is a rapid change in the composition of the gut microbiota, which becomes similar to the microbiota of a healthy donor. Each of these methods of correction demonstrates a different degree of influence on the gut microbiota, and their therapeutic effectiveness depends on the direct characteristics of the methods used, as well as the specific disease and requires further study.

Fecal microbiota transplantation is a treatment method based on the introduction of donated fecal material to the recipient in order to restore the damaged composition of the intestinal microbiota. This review summarizes existing data on indications for fecal microbiota transplantation, recommendations for donor selection, processing and storage of donor biomaterial.

Concerning the uncontrolled growth in the incidence of obesity and Type 2 Diabetes Mellitus (T2DM), numerous research have been carried out to study the pathogenetic mechanisms of progress of these diseases and development of new methods for their prevention and treatment in recent years. T2DM is known to be a multifactorial disease, in the development of which both lifestyle and various environmental factors, and genetic predisposition are involved. At the same time, in recent years, a theory has been discussed that intestinal dysbiosis, which is caused with quantitative and qualitative changes in the gut microbiota (GM) is one of the mechanisms of obesity and T2DM development. At the moment, various methods have been proposed for restoring the normal composition of GM, including the administration of prebiotics and metabiotics that stimulate the growth of gut flora, as well as probiotics, which directly include the necessary beneficial bacteria (mainly Bifidobacterium and Lactobacillus). Fecal microflora transplantation (FMT), which allows transferring an entire microbial community into the recipient's body, rather than individual bacteria is the newest and least studied method of GM normalization. In this connection, this method of GM influencing is of great interest for the prevention and treatment of metabolic diseases.

Introduction. At the present time there is increase the number of patients diagnosed with pseudomembranous colitis due to Clostridiodes difficile, respectively it significantly increases the frequency of hospitalizations, the length of hospital stay and the cost of treatment. Approved drug methods for correcting a pathological condition are not always able to lead to recovery after the first use, repeated and prolonged courses of therapy are often required, especially with recurrent Clostridiodes difficile. An alternative way of treatment is fecal microbiota transplantation from a donor. Nowadays, fecal microbiota transplantation is included in national clinical guidelines in several countries in Europe, the USA and Australia. In Russia this method has not been registered, however, there are some publications about its successful application in gastrointestinal diseases, oncohematology, and some autoimmune diseases. Aim. To show the result of successful treatment of severe pseudomembranous colitis after a single fecal microbiota transplantation.Material and methods. Outpatient treatment of an acute respiratory infection with a broad-spectrum antibacterial drug caused the development of severe pseudomembranous colitis in a young patient. Standard courses of metronidazole and vancomycin were unsuccessful. Transplantation of fecal microbiota from a donor was performed via ileocolonoscopy.Results. A single fecal microbiota transplantation contributed to the patient’s complete recovery, short term rehabilitation and the absence of recurrence of Clostridiodes difficile within two years. Conclusions. Evidence-based medicine has shown the high efficiency of fecal microbiota transplantation. In Russia a legislative basis is needed for including fecal microbiota transplantation in clinical guidelines for the treatment of severe Clostridiodes difficile resistant to standard therapy.

Background: Nowadays fecal transplantation (FT) is considered as a component of the treatment for a wide range of disorders, including autoimmune diseases (ulcerative colitis, Crohn's disease, type 1 diabetes mellitus and insulin resistance, multiple sclerosis, psoriasis). High-quality preparation of the biomaterial is a necessary procedure that allows for long-time storage of the prepared fecal transplant at ultralow temperature conditions and it use as needed.Aim: To optimize the method of preparation of the biomaterial for fecal transplantation and to evaluate its "survival" at different time points under cryopreservation conditions.Materials and methods: A device for the preparation of donor fecal material for transplantation has been developed and proposed (the Russian Federation patent No. 2659417 from July 2, 2018). Donor fecal material (collected in a sterile container on the same day of preparation in the morning), the solvent, and glycerol are homogenized automatically in the closed loop device and passed through a disposable filter with attached sterile hemocon container. Freezing at ultralow temperature (cryopreservation at -80 °C) allows for long time storage of this fecal graft. We studied the microbial composition of the obtained native substrate and samples that were cryopreserved at different time points (7 to 365 days).Results: The proposed original method makes it possible to prepare the biomaterial for storage at a low temperature mode without any contact, in a closed loop, for subsequent fecal transplantation within 6–12 months. The analysis of the fecal transplant at different time points has shown no qualitative and quantitative differences in the microbial composition between the native donor material and the freshly prepared filtrate. The biomaterial prepared according to the original method is stable for 12 months.Conclusion: The proposed hardware method for preparing the biomaterial for fecal transplantation is easy to use and allows for the preparation of a graft with minimal external microbial contamination, in contrast to the conventional method of donor material preparation by filtering fecal matter through gauze or coffee filters with manual assistance.

Aim.Was to evaluate clinical efficacy, adverse events and changes in the gut microbiome after fecal microbiota transplantation (FMT) in patients with gastrointestinal (GI) form of graft-versus-host disease (GVHD). Materials and methods.The prospective single-center study in R.M. Gorbacheva institute included 27 patients with GI GVHD after allogeneic stem cell transplantation. 19 patients received FMT, 8 patients received placebo. Clinical scales for GI autoimmune diseases were used to evaluate response. Microbiome alterations were assessed with multiplex PCR. Results.After FMT higher overall bacterial mass (р=0.00088), higher bacterial numbers ofBifidobacteriumspp. (р=0.021),Escherichia coli(р=0.049) andBacteroides fragilisgr. (р=0.000043) compared to placebo group. Also higher bacterial mass was observed in patients with clinical response (р=0.0057). The bacterial mass after procedure in non-responders was compared to the placebo group (р=0.31). Partial response of GVHD was achieved faster in the FMT group compared to placebo (median 4 days vs 48 days,p=0.014). Complete response was observed in 8 (42%), 14 (74%) and 16 (84%) at 30, 60 and 90 days respectively, while in the placebo group only 0%, 1 (13%) and 4 (50%) achieved complete response at the same time points. The incidence and severity of adverse events was comparable between FMT and the placebo group. Conclusion.FMT in patients with refractory GI GVHD was associated with favorable clinical outcomes and recovery in certain marker bacterial populations. Multiplex PCR can be used to assess an engraftment of a donor microbiota. FMT in GI GVHD was not associated with life-threatening adverse events, but further studies are required to validate clinical efficacy.

Introduction and purpose Fecal microbiota transplantation (FMT) is a process of transferring gut microflora from a healthy donor to a recipient. It is indicated that the human distal gastrointestinal tract consists of more than 1000 species of bacteria, which have an impact on local and systemic processes related to immunity, nutrition and the gut-brain axis. The growth of new bacterial species, reduction of microbial variety or big changes in the ratio between them can lead to a dysbiosis. The relationship between intestinal microbiota and some systemic diseases is seen.The study aimed to present the state of knowledge on FMT in the treatment of intestinal diseases. Publications from the last 5 years from the Pubmed database were included.A brief description of the state of knowledgeIntestinal diseases constitute the main group of indications for FMT. FMT can be delivered via upper or lower gastrointestinal routes. The review presents different studies concerning the usage of FMT. Among them, recurrent Clostridium difficile infection, colitis ulcerosa, Crohn’s disease and irritable bowel syndrome are mainly indicated in the literature. FMT might find its application also in a treatment of multidrug-resistant organisms colonization, antibiotic-associated diarrhea, gut acute graft-versus-host disease and radiation enteritis. There is a possibility of the occurrence of adverse events from the digestive tract after FMT. However, the studies evaluate them as mostly mild and transient. In some cases it was necessary to repeat FMT to achieve a satisfactory final result.ConclusionsFecal microbiota transplantation gives hope for a safe and effective method of treatment of certain intestinal diseases. There is a need for conducting further analysis of the method.

Intestinal human microbiota is a dynamic system that is under the pressures of its host organism and external factors. Microbiota disruption caused by these factors can lead to severe diseases including inflammatory and oncological diseases of the gastrointestinal tract. One of the possible approaches in managing the intestinal microbiota is fecal microbiota transplantation (FT) – transfer of the microbiota from the stool of a healthy donor to the intestinal tract of a recipient patient. Currently, this procedure is recognized as an efficacious method to normalize the intestinal microbiota mainly in inflammatory diseases of the gastrointestinal tract. In Russia, pilot studies of the effectiveness of FT in patients with ulcerative colitis have been conducted for several years, and these studies were started in Novosibirsk. The aim of this study was to assess the change of intestinal microbiome in 20 patients with ulcerative colitis after a single FT procedure. The main method is a comparative analysis of 16S ribosomal RNA sequence libraries constructed using fecal samples obtained from patients with ulcerative colitis before and after FT and sequenced on the Illumina MiSeq platform. The obtained results showed that FT led to an increase in average biodiversity in samples after FT compared to samples before FT; however, the difference was not significant. In the samples studied, the proportion of Firmicutes sequences, the major gastrointestinal microbiota of healthy people, was decreased (~32 % vs. >70 %), while the proportion of Proteobacteria sequences was increased (>9 % vs.

This literature review analyzes the role of human microbiome in cancer development. We provide the data on the most common bacteria found in patients with colon cancer: Fusobacterium nucleatum, Bacteroidеs fragilis, and some strains of Escherichia coli. Fecal microbiota transplantation is a new experimental method of introducing healthy bacterial flora into a recipient with intestinal diseases. The identification of oncogenic bacterial strains will significantly enhance our ability to diagnose and prevent colorectal cancer.

In this review, we have summarized the latest evidence, indications, and methods of fecal microbiota transplantation (FMT), and analyzed the prospects and therapeutic potentials of this procedure. In recent years, FMT has attracted great interest, especially due to the global Clostridium difficile infection (CDI). FMT is now recommended as alternative therapy for recurrent CDI when standard treatment with antibiotics fails. It involves putting suspended biomaterial with intestinal microorganisms of a healthy donor into the intestine of a patient. Although the exact mechanism of action is not entirely clear, it is believed to restore the composition and function of the intestinal microbiota in diseased patients. The efficacy varies depending on the route of administration, quality and volume of donor biomaterial, and treatment before the procedure.

Obesity is a worldwide problem of the last century, the prevalence of which has reached pandemic proportions in developed countries. Over the past few years, a considerable amount of data has been gathered, reporting a direct link between changes in gut microbiota and the development of obesity, as well as related diseases, primarily, diabetes mellitus type 2. The elaboration of optimal methods of prevention and treatment regimens of these diseases needs to structure the existing knowledge about the mechanisms of development of metabolic disorders, the role of intestinal microbiota in the latter and possible therapeutic “targets”. This review examines the role of microorganisms in the human body, with the main focus on the developmental origins of metabolic disorders using animal models and accumulated experience of research on their effects on the human body, and also discusses possible treatment options, including bariatric surgery, fecal microbiota transplantation, the use of pre- and probiotics and certain particular groups of glucose-lowering drugs.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective method to treat malignancy and some solid tumors which may be accompanied by life-threatening immune and infectious complications refractory to standard immunosuppressive and antibacterial therapy. According to literature data, fecal microbiota transplantation (FMT) may be applied to restore functional activity of microbiota and to overcome antibiotic resistance. Two clinical cases of FMT in critical ill patients who had developed acute graft-versus-host disease (aGvHD) of intestine after allo-HSCT are presented in the article. The aim of the study was to assess FMT efficiency and safety in immunocompromised critically ill patients. Results. Following FMT, a complete regress of aGvHD signs as well as reduction of systemic infectious process were registered, due to probable modulation of the immune response. In one patient, elimination from respiratory ways of carbapenemase-producing Klebsiella pneumoniae positive for NDM- and OXA-48- producing was noted, like as elimination of Pseudomonas aeruginosa synthesizing KRS-type carbapenemase. Conclusions. FMT may be considered an alternative approach to intestinal aGvHD treatment in critically ill patients after allo-HSCT.

Obesity is a global epidemic of modern times and has serious health consequences, as it is a major risk factor for the development of chronic diseases such as hypertension, type 2 diabetes, dyslipidemia, atherosclerosis and its complications. The study of risk factors, pathogenetic mechanisms, as well as the search for new methods of treatment and prevention of this pathology is an important task of modern medicine. Today it is known that the composition and function of the intestinal microbiota play a certain role in the development of obesity and a number of metabolic disorders. One of the areas of prevention of early onset and development of these diseases may be the maintenance of a normal composition and correction of disorders of the intestinal ecosystem. In this review, the currently known interrelationships of changes in the composition of the intestinal microbiota and obesity are reviewed, and studies have been analyzed to assess the composition of the adult intestinal microbiota in obesity. The presently available data on the correction of overweight and obesity by exposing the composition of the intestinal microbiota are presented.

Since Ilya Metchnikoff’s studies, both medical science and clinical practice have accumulated a large amount of evidence that human intestinal microbiota possesses a unique characteristics for our existence. However, only recently, scientists have achieved the actual breakthrough in this field of human physiology, and we start to understand the precise mechanisms of the complex interplay of microbial activity with human homeostasis and discover numerous new functions of intestinal microbes. In this regard, a novel medical technology evolves since 1958, so called fecal microbiota transplantation (FMT), which is the administration of donor feces to the patients suffering from different kinds of diseases. Such infusion of donor feces restores the natural balance of gut commensal germs. FMT is most efficacious in severe or recurrent Clostridium difficile infection. FMT has been also reported to cure diarrhea and constipation caused by different conditions, such as multiple sclerosis, Crohn ’s disease etc. In the U.S. and Canada as well as in other countries FMT is of uttermost interest of not merely clinical practitioners but lately also of regulatory authorities. The paper also addresses the possibility of application the Russian pharmaceutical legislation to FMT.

The intestinal microbiome plays a significant role in the regulation of peristalsis, exerts some influence on the functioning of the immune system, course of metabolic processes and formation of some aspects of behavior. There is evidence that maternal microflora can exert an influence on the fetus by translocation of bacteria or bacterial particles through the placental barrier, although, of course, the main colonization of the intestine of the infant occurs in the process of natural childbirth under the influence of the vaginal and intestinal flora of the mother. In children born by cesarean section the normal colonization of the gut is disturbed, which can determine a higher risk of developing in the future of some immune-mediated diseases, Type 1 diabetes mellitus and obesity. Medical men often try to adjust dysbiosis or changes in the composition of the fecal microflora called dysbiosis by the use of probiotics. In addition to the well-known effects of probiotics in the treatment of acute diarrhea in children, these drugs currently are being increasingly used for prevention of necrotizing enterocolitis of the newborn, despite the fact that evidence of the effectiveness of their routine use is not sufficient. A number of studies have shown that some probiotics may be effective in the prevention of atopic diseases, prevention and treatment of antibiotic-associated diarrhea, reducing the frequency and severity of necrotizing enterocolitis, relief of infant colic, and therapy of constipation. Given the role of microbiota in the development of obesity, some probiotics have been used and showed their effectiveness in weight loss. The fecal microflora transplantation was introduced relatively recently to treat Clostridium difficile infection and inflammatory bowel disease. In this review we discuss current data on the intestinal microbiota, its formation, functions, disturbance of the composition and possible ways of their correction.

The paper gives an update on the role of the gut microbiome (GM) in the development of nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, alcoholic liver disease, liver cirrhosis (LC), and its complications, such as hepatic encephalopathy (HE) and hepatocellular carcinoma (HCC), and discusses the possibilities of its correction with prebiotics, probiotics, synbiotics, antibiotics, and fecal microbiota transplantation (FMT). The pathophysiology of the liver diseases in question demonstrates some common features that are characterized by pathogenic changes in the composition of the gastrointestinal tract microflora, by intestinal barrier impairments, by development of endotoxemia, by increased liver expression of proinflammatory factors, and by development of liver inflammation. In progressive liver disease, the above changes are more pronounced, which contributes to the development of LC, HE, and HCC. GM modulation using prebiotics, probiotics, synbiotics, antibiotics, and FMT diminishes dysbacteriosis, strengthens the intestinal mucosal barrier, reduces endotoxemia and liver damage, and positively affects the clinical manifestations of HE. Further investigations are needed, especially in humans, firstly, to assess a relationship of GM to the development of liver diseases in more detail and, secondly, to obtain evidence indicating the therapeutic efficacy of GM-modulating agents in large-scale, well-designed, randomized, controlled, multicenter studies.

A corrigendum on «The new views on the state of the gut microbiota in obesity and diabetes mellitus type 2» by Elena V. Pokrovskaya, Minara S. Shamkhalova, Marina V. Shestakova (2019). Diabetes Mellitus. 22(3). doi: 10.14341/DM10194There is an error on the page 255: "Moreover, in obese patients, the concentration of circulating LPS increases by 20%, and in patients with diabetes mellitus, it increases by 125%. LPS is transported from cells of the large intestine into the bloodstream through chylomicrons or through intercellular gaps in the intestinal wall; by forming a complex of CD14 with Toll-like receptor 4 of macrophages and endothelial cells, it causes the release of anti-inflammatory cytokines: namely, interleukin-1, interleukin-6 and tumour necrosis factor alpha ". Instead of " pro-inflammatory cytokines" was published " anti-inflammatory cytokines ".Literary source «Dahiya DK, Renuka, Puniya M, et al. Gut Microbiota Modulation and Its Relationship with Obesity Using Prebiotic Fibers and Probiotics: A Review. Front Microbiol. 2017;8:563. doi: https://doi.org/10.3389/fmicb.2017.00563» is listed twice (№№ 7 and 13) in the list of references.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.The original article has been updated.

Fecal microbiota transplantation is a treatment method based on the introduction of donated fecal material to the recipient in order to restore the damaged composition of the intestinal microbiota. This review summarizes existing data on indications for fecal microbiota transplantation, recommendations for donor selection, processing and storage of donor biomaterial.

Aim: Was to evaluate clinical efficacy, adverse events and changes in the gut microbiome after fecal microbiota transplantation (FMT) in patients with gastrointestinal (GI) form of graft-versus-host disease (GVHD)., Materials and Methods: The prospective single-center study in R.M. Gorbacheva institute included 27 patients with GI GVHD after allogeneic stem cell transplantation. 19 patients received FMT, 8 patients received placebo. Clinical scales for GI autoimmune diseases were used to evaluate response. Microbiome alterations were assessed with multiplex PCR., Results: After FMT higher overall bacterial mass (р=0.00088), higher bacterial numbers ofBifidobacteriumspp. (р=0.021),Escherichia coli(р=0.049) andBacteroides fragilisgr. (р=0.000043) compared to placebo group. Also higher bacterial mass was observed in patients with clinical response (р=0.0057). The bacterial mass after procedure in non-responders was compared to the placebo group (р=0.31). Partial response of GVHD was achieved faster in the FMT group compared to placebo (median 4 days vs 48 days,p=0.014). Complete response was observed in 8 (42%), 14 (74%) and 16 (84%) at 30, 60 and 90 days respectively, while in the placebo group only 0%, 1 (13%) and 4 (50%) achieved complete response at the same time points. The incidence and severity of adverse events was comparable between FMT and the placebo group., Conclusion: FMT in patients with refractory GI GVHD was associated with favorable clinical outcomes and recovery in certain marker bacterial populations. Multiplex PCR can be used to assess an engraftment of a donor microbiota. FMT in GI GVHD was not associated with life-threatening adverse events, but further studies are required to validate clinical efficacy.

Inflammatory bowel diseases (IBD), which include ulcerative colitis (UC) and Crohn's disease (CD), are chronic intestinal inflammatory disorders with an unknown etiology. They are characterized by chronic recurrent inflammation of the intestinal mucosa and lead to a significant decrease in the quality of life and death of patients. IBD are associated with suppression of normal intestinal microflora, including a decrease in bacteria, producers of short chain fatty acids (SCFAs), exhibiting anti-inflammatory and protective properties. Among the various methods of intestinal microflora correction, fecal microbiota transplantation (FMT), which engrafts the fecal microbiota from a healthy donor into a patient recipient, is of a particular interest. As a result, a positive therapeutic effect is observed, accompanied by the restoration of the normal intestinal microflora of the patient. A significant drawback of the method is the lack of standardization. Metabolites produced by intestinal microflora, namely SCFAs, allow objective assessment of the functional state of the intestinal microbiota and, consequently, the success of the FMT procedure. Using gas chromatography and nuclear magnetic resonance spectroscopy techniques, we have analyzed concentrations and molar ratios of SCFAs in fecal samples of 60 healthy donors. Results were in good accord when comparing two methods as well as with published data. Analysis of SCFAs in feces of patients with UC (19 patients) and CD (17 patients) revealed a general decrease in the concentration of fatty acids in the experimental groups with significant fluctuations in the values in experimental groups compared to control group of healthy donors. On the limited group of IBD patients (6 patients with UC and 5 patients with CD) concentration of SCFAs before and within 30 days of observation after FMT was determined. It was shown that FMT had a significant impact on the SCFAs levels within 1 month term; tendency to reach characteristics of healthy donors is unambiguously traced for both diseases.

Intestinal human microbiota is a dynamic system that is under the pressures of its host organism and external factors. Microbiota disruption caused by these factors can lead to severe diseases including inflammatory and oncological diseases of the gastrointestinal tract. One of the possible approaches in managing the intestinal microbiota is fecal microbiota transplantation (FT) - transfer of the microbiota from the stool of a healthy donor to the intestinal tract of a recipient patient. Currently, this procedure is recognized as an efficacious method to normalize the intestinal microbiota mainly in inflammatory diseases of the gastrointestinal tract. In Russia, pilot studies of the effectiveness of FT in patients with ulcerative colitis have been conducted for several years, and these studies were started in Novosibirsk. The aim of this study was to assess the change of intestinal microbiome in 20 patients with ulcerative colitis after a single FT procedure. The main method is a comparative analysis of 16S ribosomal RNA sequence libraries constructed using fecal samples obtained from patients with ulcerative colitis before and after FT and sequenced on the Illumina MiSeq platform. The obtained results showed that FT led to an increase in average biodiversity in samples after FT compared to samples before FT; however, the difference was not significant. In the samples studied, the proportion of Firmicutes sequences, the major gastrointestinal microbiota of healthy people, was decreased (~32 % vs. >70 %), while the proportion of Proteobacteria sequences was increased (>9 % vs. <5 %). In some samples collected before FT, sequences of pathogenic Firmicutes and Proteobacteria were detected, including Acinetobacter spp., Enterococcus spp., Klebsiella pneumoniae, Proteus mirabilis, Staphylococcus aureus, Stenotrophomonas maltophylia, Streptococcus spp. In most cases, the proportion of such sequences after FT substantially decreased in appropriate samples. The exception was the Clostridium difficile sequences, which accounted for <0.5 % of the sequences in samples from almost half of the patients and after FT, the share of such C. difficile sequences was significantly reduced only in samples from three patients. It should be noted that the proportion of Lactobacillus spp. increased ten-fold and their species composition significantly expanded. According to the obtained results, a preliminary conclusion can be made that even a single FT procedure can lead to an increase in the biodiversity of the gastrointestinal microbiota in patients and to the optimization of the taxonomic composition of the microbiota., (Copyright © AUTHORS, 2020.)

The paper gives an update on the role of the gut microbiome (GM) in the development of nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, alcoholic liver disease, liver cirrhosis (LC), and its complications, such as hepatic encephalopathy (HE) and hepatocellular carcinoma (HCC), and discusses the possibilities of its correction with prebiotics, probiotics, synbiotics, antibiotics, and fecal microbiota transplantation (FMT). The pathophysiology of the liver diseases in question demonstrates some common features that are characterized by pathogenic changes in the composition of the gastrointestinal tract microflora, by intestinal barrier impairments, by development of endotoxemia, by increased liver expression of proinflammatory factors, and by development of liver inflammation. In progressive liver disease, the above changes are more pronounced, which contributes to the development of LC, HE, and HCC. GM modulation using prebiotics, probiotics, synbiotics, antibiotics, and FMT diminishes dysbacteriosis, strengthens the intestinal mucosal barrier, reduces endotoxemia and liver damage, and positively affects the clinical manifestations of HE. Further investigations are needed, especially in humans, firstly, to assess a relationship of GM to the development of liver diseases in more detail and, secondly, to obtain evidence indicating the therapeutic efficacy of GM-modulating agents in large-scale, well-designed, randomized, controlled, multicenter studies.

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.