This study assessed the metabolome and peptidome profiles of various fermented milk products produced using different starter cultures. Milk fermentation involves a set of macromolecular decomposition reactions performed by microorganisms under controlled conditions. Biotransformation of fats, proteins, and carbohydrates shapes the metabolome profile of each fermented product. Many of these microbe-generated molecules exhibit biological activities that can affect human health. The resulting profile is unique for every fermented product and depends on technology, raw materials, and starter culture composition. We used four non-targeted metabolomic methods to assess semi-quantified concentrations of four types of molecules in the final products: peptides; amino acids; long-, medium-, and short-chain fatty acids; mono- and disaccharides and their derivatives. Ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) was performed on the peptidome. For all other fractions, we used gas chromatography–mass spectrometry (GC-MS), with a method adapted to specific metabolite conditions. Metabolome and peptidome of four groups of 15 dairy cow milk products including yogurt (Y), fermented milk (FM), kefir made with commercial cultures (K) and kefir made with grains (KG) was performed on days 7 and 14 of shelf life at 4°C, and milk (M) was used as a control. Peptides, amino acids, fatty acids, mono- and disaccharides, and their low molecular weight derivatives were evaluated. In total, 348 peptides, 37 amino acids, 25 fatty acids, and 23 mono- and disaccharides were identified in the products. Among them, 41 functional peptides, branch-chained amino acids (BCAA), orotic acid (vitamin B13), d-phenyllactic acid, 5-phenylvaleric acid and myo-inositol (vitamin B8) accumulated in fermented products during storage. ### Competing Interest Statement The authors have declared no competing interest. Human & Nutrition LLC

Introduction. The microbiota of the oral cavity and oropharynx, actively interacts with the epithelium of the mucous membrane and the immune system, creates antagonistic conditions for the growth and reproduction of pathogens. Microbiocenosis-preserving therapy can provide conditions for maintaining colonization resistance and reduce the likelihood of adhesion of respiratory viruses.Aim. To evaluate the effect of local use of various antimicrobial drugs on the microbiota of the oropharyngeal mucosa in children with acute respiratory infection.Materials and methods. 120 children (5–10 years old) with acute respiratory infection were divided into three groups, in which they were used as part of complex therapy: in group 1st – hexetidine-containing aerosol, in group 2nd – a children’s spray containing gramicidin S and cetylpyridinium chloride, in the 3rd – 0.01% solution of benzyldimethyl-myristoylamino-propylammonium. On the 1st and 12th days of observation, participants had a throat swab taken to study the state of the oropharyngeal microbiota using 16S rRNA sequencing. The results obtained were compared with those of healthy peers.Results. According to sequencing data, the microbiota of participants in all groups before treatment differed from the microbiota of healthy peers in terms of alpha and beta diversity, as well as in the results obtained by the nearest balance method. Local use of antiseptic drugs influenced the microbiota at the level of species and genera of microorganisms. After treatment in the 2nd group, in contrast to the 1st and 3rd, statistically significant changes in the balances at the level of microorganism species were revealed towards the indicators of healthy peers.Conclusions. A combined drug containing cetylpyritinium chloride and the bacteriocin-like antimicrobial peptide gramicidin S demonstrated no negative effect on commensal microbiota and contributed to the stabilization of the regional microbiota.

Current omics methods, which are essential for scientific research, are overviewed. These methods enable studies of the mechanisms of clinical manifestations by analyzing the relationship between the microbiota characteristics and clinical parameters. To represent the complex interactions between the microbiome and host metabolism, metagenomics and metabolomics techniques that contribute to the search for new therapeutic approaches are most relevant. Based on the metagenomic data, the associated taxa are searched, and the metabolic profile indicates the result of the activity of the microbial community. The characteristics of technologies for studying metagenomes using the amplicon sequencing method are considered, and the depth of identification of microorganisms, the level of sequencing errors and the preference in terms of cost are evaluated. Studying the evolution of pathogens and metabolic processes, expressed genes, and determinants of antibiotic resistance contributes to the development of rational strategies for disease therapy and control of the spread of infectious diseases. In recent years, the number of scientific projects in the field of microbiota research has been steadily increasing, which necessitates the need to raise physicians' awareness of modern methods and research approaches in order to apply relevant data in practical work.

Introduction. Mother’s breast milk is considered to be the best source of infant nutrition and, paradoxical as it may sound, the only product of the infant diet, which composition is still poorly known to us. This article presents the findings of a study on the breast milk microbiota conducted in the Russian Federation for the first time.Aim. To study the composition of the breast milk microbiota of healthy women living in the Russian Federation and identify the impact of various factors on its diversity.Materials and methods. A molecular genetic study on 56 colostrum samples and 12 mature breast milk samples from 56 healthy donors using a method based on sequencing of bacterial 16S rRNA gene was conducted.Results. In a batch of 56 colostrum samples, 22 species and 242 genera of bacteria were identified. Firmicutes, Proteobacteria, Actinobacteriota were the most predominant species of bacteria in healthy women with a normal body mass index, from a physiological pregnancy, who did not take antibiotics, after natural delivery at term; Streptococcus, Staphylococcus and Gemella were the most predominant at the level of delivery. Statistical analysis of the impact of nationality, age, number of children in the family and duration of hospitalization (PERMANOVA) showed no significant differences in the proportions of bacteria in the colostrum of women (p > 0.05). The gender of the child was the only factor that turned out to be significant. The biodiversity of colostrum of girl-delivered mothers were higher (Shannon index) than that of boy-delivered mothers. In addition, the mature breast milk microbiota (1 month after delivery) has lower alpha diversity as compared to colostrum.Discussion. The analysis of our results and reports from foreign colleagues showed significant similarities and differences, which, certainly, were explained by a number of reasons related to methodological and geographical differences, the method, timing and even the time of day when breast milk samples were collected.Conclusion. In general, the colostrum of healthy women had a fairly stable bacterial composition, and its rich biodiversity fully demonstrated high quality of the first microbial inoculum for the newborn intestine. Our results provide valuable insights into the healthy breast milk microbiota in women living in the Russian Federation and can be used as reference ranges, as well as for comparison with similar indicators in women from other countries.

Introduction. Acute respiratory infections cover majority of pediatric outpatient visits and hospitalizations, especially during the cold and flu epidemic season. Aim. To evaluate the effect of Baс-Set Cold/Flu probiotic on the clinical manifestations and severity of acute respiratory infections (ARI) along with standard symptomatic therapy during periods of increased morbidity (November 2023 – March 2024). Materials and methods. This study was an open-label, observational, multicenter study. The number of subjects was 234: 111 volunteers in the first group (experimental) and 123 volunteers in the second group (control) aged from 2 to 10 years inclusive (mean age 5.79) with a diagnosis of ARI. Patients of the first group took Bac-Set Cold/Flu probiotic along with standard symptomatic therapy in comparison with control group which took a standard symptomatic therapy only. Statistical analysis was performed using the R programming language. Results and discussion. The use of probiotic significantly reduced the number of complications and the prescription of antibiotic therapy by more than three times (5% in the probiotic group versus 17% in the control group). A significant difference was revealed in the total duration of the disease (the maximum period from the first symptom of fever to the fact of complete recovery, – absence of fever within last 48 hours) between groups (Mann- Whitney test, p-value = 0.017). In the experimental group, the average duration of illness was 6.2 ± 3.7 days, in the control group – 7.2 ± 3.1 days. A statistically significant difference in the duration of fever was also revealed (Mann-Whitney test, p-value = 0.006). In the control group, on average, fever lasted 1 day longer. The median maximum temperature in the probiotic group was 0.5 degrees lower at the 2nd visit compared to the control group. The use of the probiotic did not affect the symptoms of cough, nasal congestion and the color of nasal discharge, but a trend was recorded for the effect on the symptoms of sore throat. Conclusion. The use of a probiotic reduced the number of complications and the prescription of antibiotic therapy by more than three times, the duration of the disease and fever.

Background. Intestinal microbiota is one of the most important factors determining the state of human health, including its influence on the immunological mechanisms regulating the development of allergic diseases in childhood. The role of intestinal microbiota and the gut – lung axis in the development of bronchial asthma (BA) is an important area of research.Aim. To analyze the taxonomic composition of intestinal microbiota in children with BA using 16S rRNA gene sequencing.Materials and methods. The study included patients with BA (n = 50, mean age 10.34 ± 2.99 years) and a group of apparently healthy individuals (n = 49, mean age 10.3 ± 2.8 years). For all patients, medical history was taken, and physical examination and stool test were performed. Patients with BA were assessed for the level of total and specific immunoglobulin (Ig) E and underwent spirometry. The microbiota composition was analyzed by 16S rRNA gene sequencing with subsequent bioinformatic and statistical analysis.Results. Significant differences in the composition of the intestinal microbiota (beta diversity) and a decrease in taxonomic diversity (alpha diversity) were found in patients with BA compared to healthy controls. The intestinal microbiota of patients with BA was characterized by an increase in the abundance of Bacteroides, Parabacteroides, Lachnospira, Roseburia, Akkermansia, Anaerostipes, Sutterella, Odoribacter, Phascolarctobacterium, Butyricimonas, as well as unclassified bacteria from the Rikenellaceae families. The intestinal microbiota of children without BA was characterized by greater abundance of bacteria from Blautia, Bifidobacterium, Dorea, Ruminococcus, Streptococcus, Eubacterium, Acinetobacter, Collinsella, Lactococcus, Catenibacterium genera and unclassified bacteria from the Clostridiaceae and Coriobacteriaceae families. Significant differences in the quantitative abundance of bacteria were revealed depending on the type of sensitization, the level of total IgE, and the value of FEV1.Conclusion. The results obtained indicate the differences in the intestinal microbiota composition in children with BA and healthy children.

Infantile functional gastrointestinal disorders, such as colic, constipation, diarrhea, and gastroesophageal reflux (regurgitation), often occur in early infancy and, representing one of the causes of significant parental anxiety, lead to a significant strain on the healthcare resources. In this study, we aimed to evaluate the effects of Lactobacillus reuteri drops (L. reuteri NCIMB 30351) on the symptoms of infantile colic, constipation, diarrhea, and gastroesophageal reflux, as well as on the levels of intestinal microbiota in full-term newborns during the first months of life. A randomized, placebo-controlled, single-masked (blinded), post-marketing clinical study was conducted in two clinical units—Children’s City Clinical Hospital of Moscow and Medical Center “St. Andrew’s Hospitals-NEBOLIT” from March 2020 to May 2022 in 90 infants aged from 1 to 4 months (mean age (± SD) 12.3 ± 5.09 weeks; 53.3 ClinicalTrials.gov : NCT04262648.

This letter is about a particular case of approximation of a compositional vector by the nearest balance—its application to principal balance analysis (PBA). It compares two methods: our NearestBalance approach (1) and the constrained method suggested previously in references 2 and 3. We recognize that they have the same underlying idea, and we apologize for having missed this fact in our original paper. Still, due to algorithmic details the constrained method provides a suboptimal solution, while the NearestBalance approach guarantees the minimization of the approximation error.

Background. The oropharyngeal microbiota is important in maintaining resistance, eliminating viruses and regulating local protective reactions in response to inflammation in acute respiratory infections. Aim. To evaluate of the effect of topical etiotropic therapy on clinical manifestations, elimination of viruses and on oropharyngeal microbiota in the treatment of acute infectious inflammation of the throat that occurred as part of acute respiratory infections in children aged 510 years. Materials and methods. 120 outpatient patients randomized into 3 equal groups were treated for 7 days: in Group 1 0.2% hexethidine-containing aerosol, in Group 2 0.03 mg combined spray gramicidin S and 0.1 mg cetylpyridinium chloride, in Group 3 0.01% topical solution containing benzyldimethyl-myristoylamino-propylammonium. Changes in the severity of clinical manifestations were compared (integral indicator modified Tonsillopharyngitis Severity Score TSSm for children, the severity of the "sore throat" symptom on the WongBaker scale, the severity of local signs of inflammation according to pharyngoscopy data) in groups at Visit 2 (day 51) and Visit 3 (day 121) compared with the Visit 1. The elimination of acute respiratory infection pathogens was evaluated: polymerase chain reaction (PCR) of oropharyngeal smears obtained on days 1, 3 and 5 (1) PCR-1, PCR-2, PCR-3 respectively, with the detection of 12 respiratory viruses, including SARS-CoV-2. The state of the microbiota was assessed by sequencing the full-size 16S gene in samples obtained before and after treatment 1st and 12th (1) days, and compared with 19 indicators in healthy. Results. By Visit 3, the decrease in TSSm indicators was: 4.01.07 in Group 1; 5.01.48 in Group 2 and 4.01.02 in Group 3. The intergroup differences between Group 2 and 1, Group 2 and 3 were statistically significant (p0.05). The severity of sore throat by Visit 3 decreased in groups 1, 2 and 3 respectively by 2.00.90, 2.50.61 and 2.10.60, intergroup differences between groups 2 and 1, 2 and 3 had statistical significance at p0.05. The time to achieve complete relief of the disease according to the TSSm indicator was (day, MSE): 16.61.47 in Group 1; 11.91.13 in Group 2 and 12.41.38 in Group 3, intergroup differences (groups 1 and 2) are significant, p0.05. The time of complete relief from sore throat for groups 13 was 12.60.96, 8.00.87 and 9.41.01 respectively, intergroup differences (groups 1 and 2) were significant, p0.05. By Visit 2, the proportion of patients with a negative PCR result increased in Group 1 by 25%, in Group 2 by 43% and in Group 3 by 38%, which corresponded to the elimination of 81, 92 and 74% of viruses detected in groups according to PCR-1 and PCR-2. The microbiota of participants in all groups before treatment differed from the microbiota of healthy in terms of alpha and beta diversity, as well as in terms of indicators obtained by the NearesBalance method. After completion of treatment, changes in the microbiota in terms of beta diversity were observed in all groups compared to the initial state. In contrast to groups 1 and 3, in Group 2 there were statistically significant changes in species-level balances between groups of microbes that distinguish between sick and healthy, towards indicators of healthy. Conclusion. Topical etiotropic medications provide rapid relief of complaints and local signs of inflammation in the treatment of patients aged 510 years with sore throat in acute respiratory infections and contribute to the rapid elimination of pathogens of acute respiratory infections. A combined preparation containing an antiseptic and a bacteriocin-like antimicrobial peptide gramicidin S provides a more pronounced therapeutic effect at an earlier time and the elimination of 90% of all respiratory viruses, including SARS-CoV-2, by the fifth day of therapy, and also has the most sparing effect on the oropharyngeal microbiota compared to antiseptic monopreparations, which may explain its more pronounced anti-inflammatory effect.

Maintaining equilibrium of the gut microbiome is crucial for human health. Diet represents an important and generally accessible natural channel of controlling the nutrients supply to the intestinal microorganisms. Although many studies showed that dietary interventions can specifically modulate gut microbiome composition, further progress of the approach is complicated by interindividual variability of the microbial community response. The reported causes of this variability include the baseline microbiome composition features, but it is unclear whether any of them are intervention-specific. Here, we applied a unified computational framework to investigate the variability of microbiome response measured as beta diversity in eight various dietary interventions using previously published 16S rRNA sequencing datasets. We revealed a number of baseline microbiome features which determine the microbiome response in an intervention-independent manner. One of the most stable associations, reproducible for different interventions and enterotypes, was a negative dependence of the response on the average number of genes per microorganism in the community-an indicator of the community functional redundancy. Meanwhile, many revealed microbiome response determinants were enterotype-specific. In Bact1 and Rum enterotypes, the response was negatively correlated with the baseline abundance of their main drivers. Additionally, we proposed a method for preliminary assessment of the microbiome response. Our study delineats the universal features determining microbiome response to diverse interventions. The proposed approach is promising for understanding the mechanisms of gut microbiome stability and improving the efficacy of personalised microbiome-tailored interventions.

Linking microbiome composition obtained from metagenomic or 16S rRNA sequencing to various factors poses a real challenge. The compositional approach to such data is well described: a so-called isometric log-ratio (ILR) transform provides correct treatment of relative abundances. Most existing compositional methods differ in the particular choice of the transform. Although this choice does not influence the prediction of a model, it determines the subset of balances between groups of microbial taxa subsequently used for interpreting the composition shifts. We propose a method to interpret these shifts independently of the initial choice of ILR coordinates by the nearest single-balance shift. We describe here application of the method to regression, classification, and principal balance analysis of compositional data. Analytical treatment and cross-validation show that the approach provides the least-squares estimate of a single-balance shift associated with a factor with possible adjustment for covariates. As for classification and principal balance analysis, the nearest balance method provides results comparable to other compositional tools. Its advantages are the absence of assumptions about the number of taxa included in the balance and its low computational cost. The method is implemented in the R package NearestBalance. IMPORTANCE The method proposed here extends the range of compositional methods providing interpretation of classical statistical tools applied to data converted to the ILR coordinates. It provides a strictly optimal solution in several special cases. The approach is universally applicable to compositional data of any nature, including microbiome data sets.

Cardiac surgery remains a field of medicine with a high percentage of postoperative complications, including infectious ones. Modern data indicate a close relationship of infectious disorders with pathological changes in the composition of the gut microbiome; however, the extent of such changes in cardiac surgery patients is not fully clarified. In this prospective, observational, single center, pilot study, 72 patients were included, 12 among them with the infectious complications. We analyzed the features of the fecal microbiota before and in the early postoperative period, as one of the markers for predicting the occurrence of bacterial infection. We also discovered the significant change in microbial composition in the group of patients with infectious complications compared to the non-infectious group before and after cardiac surgery, despite the intra-individual variation in composition of gut microbiome. Our study demonstrated that the group of patients that had a bacterial infection in the early postoperative period already had an altered microbial composition even before the surgery. Further studies will evaluate the clinical significance of the identified proportions of individual taxa of the intestinal microbiota and consider the microbiota as a novel target for reducing the risk of infectious complications.

Probiotics and vitamins can impact immune responses and modulate gut microbiome. We evaluated the effects of consuming a yogurt fortified with vitamins and probiotic Lacticaseibacillus casei and rhamnosus on upper respiratory tract infections frequency and gut microbiome during a 3-month intervention. The study included 2 case groups (consuming different flavours) and a placebo group of healthy adults (n = 158–160 in each group). The effects on URTI-related parameters in both case groups were gender-specific. The female subjects had lower URTI incidence and frequency, while for the males no significant differences were found. The URTI duration was shorter in one of the probiotic groups for females and in both such groups - for males. The observed changes in microbiome composition, blood and stool parameters were not different from those observed in the placebo group. Consumption of fortified fermented dairy foods is promising for improving immunity status within the general population.

Purpose of the study: to describe the composition of the microbiota of the initial sections of the small intestine in patients with severe necrotizing acute pancreatitis. Objectives of the study: 1. Determine the composition of the microbiota of the initial sections of the small intestine upon admission to the ICU; 2. Determine the differences in the composition of the microbiota of the initial sections of the small intestine, depending on the timing of the onset of the disease. Introduction. Disturbance of intestinal homeostasis is a leading factor in the pathogenesis and progression of systemic inflammation in patients with severe acute pancreatitis. The development of systemic complications occurs due to both mesenteric hypoperfusion and dysregulation of intestinal motility, and the destruction of the intestinal barrier, with the translocation of bacterial bodies and their substrates. Which increases the risk of developing POI and increasing mortality. With the advent of methods for high-throughput sequencing of microbiome samples - for example, in the 16S rRNA format - the possibilities for studying the structure of microbial communities have significantly expanded. In this regard, there is more and more evidence of the relationship between the state of human health and microflora inhabiting various parts of the body. Materials and methods. The study included 7 patients with a diagnosis of severe necrotizing acute pancreatitis (6 men, 1 woman), the mean age was 54.1 {+/-} 14.4 years. The patients were divided into two groups. Group 1 (n = 4) included patients admitted 2-4 days after the onset of a pain attack. Group 2 (n = 3) - patients admitted no later than 24 hours from the onset of the disease. The bacterial composition of jejunal wash samples was studied using 16S RNA sequencing. The severity of the condition was assessed using the integral scales APACHE II, SOFA, SAPS II. In patients of the main group, APACHE II was 22 {+/-} 2.83 points (18; 24), SOFA - 6.8 {+/-} 0.5 points (6; 7), SAPSII - 32.9 {+/-} 6.4 points (24.7; 40), in patients of the comparison group, APACHE II is 18.0 {+/-} 3.7 points (12; 22), SOFA - 4.0 {+/-} 2.6 points (2; 7), SAPSII - 24.4 {+/-} 5.0 points (20.9; 30.1). Material was collected at the time of installation of a sterile multifunctional intestinal catheter for Treitz's ligament, no later than 12 hours from the moment of admission to the ICU. At the time of sampling, patients were not receiving antibiotic therapy. Results. A more severe course was associated with a reduced representation in the microbiome of the species Nesseria mucosa and Parvimonas micra inhabiting the mucosal layer, as well as Megasphaera micronuciformis. The share of Streptococcus genera (S. rubneri / parasanguinis / australis species) and Actinomyces and a number of genera from the Enterobacteriaceae family in such patients, on the contrary, was higher.

The intestinal microbiota (IM) plays an important role in maintaining homeostasis in the human organism. Changes in the IM are associated with many diseases, for example, IM is involved in the pathogenesis of inflammation during acute intestinal infections (AIIs). Medications have different effects on the quantitative and qualitative composition of the microbial community and can therefore indirectly affect the course of recovery. Objective. To evaluate the IM composition in the acute period of infectious diarrhea in children and to assess the effect of therapy with nifuroxazide and cephalosporins on it. Patients and methods. This study included 21 children with invasive AIIs. Twelve patients received nifuroxazide (IN group), whereas 9 patients were treated with third-generation cephalosporins (IC group). There was also a control group comprised of 10 healthy children (group C). The duration of the course of antibacterial therapy was 5–7 days. We analyzed the microbial composition of fecal specimens from all study participants using 16S rRNA gene high-throughput sequencing. Data analysis was performed using the Knomics-Biota platform and the R Programming Environment. Results. We observed reduced alpha diversity (an integral characteristic of a microbial community which estimates the number of species in it and their proportion) already in the early period of invasive AII in children. We also found an increased total proportion of opportunistic bacteria in children with AIIs compared to controls, particularly species of Fusobacteriacea. Restoration of alpha diversity was achieved only in patients receiving nifuroxazide. Differences in the dynamics of the proportion of opportunistic microflora in the intervention groups were associated with the initial differences in the microbiome composition between the groups due to small number of patients in them. In the IN group, the proportion of Fusobacteriaceae species before treatment was higher than that in healthy controls; however, immediately after treatment completion and one month later, there were no differences in the IM composition between the IN group and controls. Patients from the IC group had higher proportion of opportunistic bacteria than healthy children; by the end of the treatment course, this parameter was normalized and was similar to that in the control group. Conclusion. The use of nifuroxazide in children with invasive AIIs was associated with restoration of alpha diversity and the reduction in the proportion of opportunistic species (in particular, Fusobacteriaceae). Children receiving cephalosporins also demonstrated the reduction in this proportion, but their alpha diversity was not restored. Keywords: acute intestinal infections, children, antibacterial therapy, nifuroxazide, cephalosporins, intestinal microbiota, 16S rRNA gene sequencing

The production of experimental beer and cider products has increased, worldwide. The complex microbiomes found in these beverages affect their organoleptic qualities and chemical compositions and can have diverse impacts on human health. The total diversity of a microbiome can be elucidated through the use of high throughput sequencing and comprehensive data analysis tools. We analysed the bacterial and yeast microbiomes found in mixed and spontaneously fermented beers (n = 14) and unpasteurised apple ciders (n = 6), using high-throughput 16S rRNA and internal transcribed spacer (ITS) sequencing. The ratio of bacteria to yeast was measured using quantitative polymerase chain reaction (qPCR), and short-chain organic acids were analysed using high-performance liquid chromatography (HPLC). An upgraded version of the Knomics-Biota system was used to analyse the data. The microbiomes included both starter microorganisms and those that originate from the production environment and the raw materials. In addition to the common Saccharomyces and Brettanomyces, the yeast diversity included many non-conventional species. The bacterial community in beer was dominated by Lactobacillus species, whereas these communities were more diverse in cider. Lactobacillus acetotolerans was prevalent in wild ales, whereas Candida ethanolica was prevalent in cask-matured beverages. We observed complex patterns of subspecies-level yeast diversity across beer styles, breweries, and countries. Our study represents an exploratory analysis of non-conventional beer and cider microbiomes and metabolomes, which contributes information necessary to develop improved quality control processes and may drive innovative product development in experimental and artisanal brewing.

Background Viliuisk encephalomyelitis (VE) is a rare endemic neurodegenerative disease occurring in the Yakut population of Northeastern Siberia. The main clinical features of VE are spasticity, dysarthria, dementia, central paresis and paralysis, and cortical atrophy observed via MRI. Many hypotheses have been proposed regarding its etiology, including infectious agents, genetics, environmental factors, and immunopathology. Each of these hypotheses has been supported to some extent by epidemiological and experimental data. Nevertheless, none of them has been decisively proven. Gut microbiome is one of the factors that might be involved in VE pathogenesis. Results Here we performed a pilot survey of the stool microbiomes of Yakut subjects with VE (n = 6) and without VE (n = 11). 16S rRNA sequencing showed that in comparison with the control group, the Yakuts with VE had increased proportions of Methanobrevibacter and Christensenella , which are reported to be linked to body mass index, metabolism, dietary habits and potentially to neurodegenerative disorders. The identified associations suggest that the microbiome may be involved in VE. Overall, the Yakut microbiome was quite specific in comparison with other populations, such as metropolitan Russians and native inhabitants of the Canadian Arctic. Conclusions Describing the gut microbiome of indigenous human populations will help to elucidate the impact of dietary and environmental factors on microbial community structure and identify risks linked to the lifestyles of such groups as well as endemic diseases.

MOTIVATION:The resistance of bacterial pathogens to antibiotics is one of the most important issues of modern health care. The human microbiota can accumulate resistance determinants and transfer them to pathogenic microbiota by means of horizontal gene transfer. Thus, it is important to develop methods of prediction and monitoring of antibiotics resistance in human populations.RESULTS:We present the agent-based VERA model, which allows simulation of the spread of pathogens, including the possible horizontal transfer of resistance determinants from a commensal microbiota community. The model considers the opportunity of residents to stay in the town or in a medical institution, have incorrect self-treatment, treatment with several antibiotics types and transfer and accumulation of resistance determinants from commensal microorganism to a pathogen. In this model, we have also created an assessment of optimum observation frequency of infection spread among the population. Investigating model behavior, we show a number of non-linear dependencies, including the exponential nature of the dependence of the total number of those infected on the average resistance of a pathogen. As the model infection, we chose infection with Shigella spp., though it could be applied to a wide range of other pathogens.AVAILABILITY AND IMPLEMENTATION:Source code and binaries VERA and VERA.viewer are freely available for download at github.com/lpenguin/microbiota-resistome. The code is written in Java, JavaScript and R for Linux platform.SUPPLEMENTARY INFORMATION:Supplementary data are available at Bioinformatics online.