Alexandra Nekrasova

The introduction of diazabicyclooctane-based inhibitor-protected β-lactams into clinical practice has significantly expanded the treatment options against infections caused by carbapenemase-producing Gram-negative bacteria. Nevertheless, the actual clinical progress has been limited due to the rapid development and spread of resistance to the new drugs. This review summarizes and analyzes current data on the mechanisms of resistance to inhibitor-protected β-lactams.

The gastrointestinal tract (GIT) microbiome is known to significantly impact on human health and be involved in many metabolic processes. The composition of the intestinal microbiota is variable and depends on both endogenous and exogenous factors. Regional climatic and geographical factors influencing the composition of the intestinal microbiota have not been characterized for the population of the Russian Federation (RF). 39% of Russia’s area is in the taiga zone, 13% in the arctic desert, tundra, and forest-tundra zones, 6% in the mixed forest zone, 8% in the forest-steppe and deciduous forest zone, 5% in the steppe zone, 1% in the semi-desert zone, and 2% in the desert zone. Each climate zone is characterized by unique climatic conditions, so when assessing the composition of the intestinal microbiota of Russian residents, it is crucial to pay attention to the regional aspect as one of the key factors influencing on changes in the composition of the human microbiome. In addition to climatic and geographical factors, there are also cultural and socio-economic factors, which is confirmed by the results of many global population studies.The aim of the study. Systematization of key exogenous factors shaping the gut microbiome: geographic features, urbanization level, climate conditions, and ethnic and national dietary patterns. Experts consider these factors when determining the relative norm for the composition of the human gut microbiota, diagnosing dysbiosis in both indigenous and non-native populations. Material and Methods. This review is based on scientific studies published over the past ten years and presented in the PubMed, Google Scholar, Scopus, Web of Science, and eLIBRARY.RU databases.Conclusion. The review reveals the influence of region of residence on the intestinal microbiota parameters of relatively healthy individuals living in various climatic zones and areas with different levels of urbanization, which can be used to determine the normal flora for residents.Contribution: Nekrasova A.I. – text editing, collection, analysis, processing of materials, systematization and generalization of literature data; Kalashnikova I.G. – collection of material and processing of literature data, text editing; Makarov V.V. – text editing, concept and design of the review and analytical research; Zhernov Yu.V. – text editing, concept and design of the review and analytical study. All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version.Conflict of interest. The authors declare no conflict of interest.Funding. The study had no sponsorship.Received: October 2, 2025 / Revised: November 18, 2025 / Accepted: November 19, 2025 / Published: January 15, 2026

Introduction. Carbohydrates, including dietary sugars and prebiotic oligo- and polysaccharides, can influence on the functional activity of probiotic bacteria by modulating their metabolic processes. An important property of prebiotics is the selective activation of endogenous protective populations of intestinal microflora, which helps to suppress the growth of pathogenic and opportunistic microorganisms. However, the specificity of various prebiotic supplements for specific exogenous probiotic microorganisms remains unclear. Probiotics can be components of a wide range of foods and dietary supplements, so it is important to understand how various nutritional substrates influence on their metabolic and functional activity. This knowledge will enable the development of more effective products and supplements aimed at maintaining intestinal bacterial balance. ”In vitro” studies allow evaluating the effects of individual components on probiotic strains. In this work, the effect of various carbohydrate substrates on the antagonistic activity of exogenous probiotic strains Lactobacillus paracasei and Bifidobacterium longum against a number of opportunistic microorganisms was studied.Objective — to study the effect of various carbohydrate substrates, including well-known prebiotics, on the antagonistic activity of probiotic strains studied against opportunistic pathogens. The choice of a carbohydrate that improves the competitive properties of probiotic strains of L. paracasei and B. longum.Materials and methods. The antagonistic activity of two probiotic strains against seven pathogenic microorganisms was studied in the presence of nine different carbohydrate substrates using a two-stage cultivation method in a combined system.Results. Probiotic strains were established to exhibit selective antagonistic properties against the same pathogen, depending on the presence of a particular carbohydrate source. For example, lactose and sucrose were found to contribute to an increase in the degree of antagonistic activity of lactobacilli against Staphylococcus aureus from moderate to high relative to the control and other substrates, and inulin and FOS suppress the competitive properties of this strain relative to Pseudomonas aeruginosa. The studied strain of Bifidobacterium longum exhibits moderate antagonistic activity against E. coli and C. jejuni, however, a number of substrates (sucrose, mannitol, inulin, chitosan) are capable of inhibiting this property. At the same time, substrates such as lactose, maltose, sucrose, chitosan, and N-acetyl-D-glucosamine increase antagonistic activity from low to moderate against K.pneumoniae, P.aeruginosa, and A.baumannii. Based on the data obtained, it can be assumed that N-acetyl-D-glucosamine (NAG), mannitol, maltose, and lactose are of interest as substrates that increase the antagonistic potential of the studied strains against a number of opportunistic pathogens.Limitations. Antagonistic activity in co-cultivation of probiotic strains has not been studied. It is also difficult to assess the functional properties of the studied strains depending on the prebiotic in the gastrointestinal tract. In addition, the effect of the concentration of carbohydrate substrates used in the work on the antagonism of target probiotic strains has not been studied.Conclusion. We have identified a significant effect of the carbohydrate component on the antagonistic properties of the probiotic strains studied, which can be further taken into account in the development of probiotic compositions, synbiotics, and functional foods.Compliance with ethical standards. The study does not require the submission of a conclusion from the biomedical ethics committee or other documents.Contribution: Kalashnikova I.G. – concept and design of research, collection of material and data processing, writing text, conducting research; Nekrasova A.I. – concept and design of research, editing; Gritsyuk O.V., Fedets Z.E., Pankova M.N. – conducting research, methodology development; Zagainova A.V. – providing research, project administration; Zhernov Yu.V., Makarov V.V. – definition of the concept, attraction of financing, provision of research; Yudin S.M. – attraction of financing, provision of research. All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version.Conflict of interest. The authors declare no conflict of interest.Funding. The work was performed within the framework of the state task No. 388-00154-22-00 “Creation of micellar probiotics of a new generation for targeted changes in the composition of the human microbiota in chronic non-communicable diseases”.Received: October 2, 2025 / Revised: November 24, 2025 / Accepted: December 2, 2025 / Published: January 15, 2026

Background: Cardiovascular diseases remain a leading cause of death worldwide, yet the prevalence of pathogenic and likely pathogenic genetic variants associated with them is still underassessed in some populations. This study aimed to assess the frequency and geographic distribution of such variants within a representative sample of the Russian population. Additionally, it explored potential links between genotype and phenotype in a cohort of long-lived adults. Methods: We analyzed whole-genome sequencing data from 75,144 adults and 2,872 individuals aged 90 and older. Variants within 37 ACMG v3.1 genes were examined using InterVar, focusing on nonsynonymous variants and indels across exons and splicing sites. Variants were grouped based on ClinVar (as of 24 April 2023) annotations, with most subjected to manual review to confirm their significance. Results: Among the adult participants, 3,817 (5.1%) carried at least one of the variants under consideration. Of these, 141 (0.19%) carried pathogenic, 580 (0.77%) likely pathogenic, and 3,127 (4.16%) variants of uncertain significance. Variants not registered in ClinVar were found in 1,782 individuals (2.37%). Notably, one participant with cardiomyopathy carried a heterozygous TTN variant. In the long-lived cohort, 15 variants were classified as pathogenic or likely pathogenic, alongside 72 uncertain variants; overall, 19 individuals (0.66%) carried pathogenic or likely pathogenic variants. No significant difference was observed in variant frequency between the adult and long-lived groups. Conclusions: This study provided essential insights into the prevalence and geographic distribution of cardiovascular disease-related variants in Russia, laying the foundation for targeted genetic screening disease prevention strategies within this population.

BACKGROUND: Gut microbiota and vitamin D may be instrumental in the development of atopic responses (atopic dermatitis, allergic rhinitis, allergic asthma, and food allergies) in children. Various diseases or immune pathologies, in particular atopic dermatitis and food allergies, are among manifestations of an imbalance in the composition of gut microorganisms. On top of that, vitamin D is a significant contributor both to modulating the gut microbiome composition and to diverse immune responses from innate and adaptive immunity, which affords ground for studying the relationship between these aspects in the context of the development of atopic conditions. So far, the relationship between the gut microbiota, vitamin D, and the development of these conditions in children has not been sufficiently explored. AIM: To study the relationship between the gut microbiota imbalance and immune disorders, in particular the development of food allergies and atopic dermatitis in children; to identify the relationship between bacterial signatures and vitamin D concentrations in children with atopic dermatitis and food allergies. METHODS: The 16S ribosomal ribonucleic acid gene of 150 fecal samples from children aged 3 to 12 years was sequenced. The concentration of vitamin D in the participants’ blood serum was determined using enzyme-linked immunosorbent assay. Thereafter, the relationship between certain bacterial signatures and serum 25(OH)D concentration was characterized through the use of statistical models (regression tree, correlation analysis, and linear regression). RESULTS: In all mathematical models used, vitamin D concentration turned out to be associated with bacterial families important for atopy, such as Lachnospiraceae, Ruminococcaceae, and Sutterellaceae. The results showed that dysbiosis coupled with vitamin D deficiency is typical of the atopic profile, which may indicate the influence of these conditions on the immune system imbalance toward the Th2 response and, consequently, on the development of allergic conditions. CONCLUSION: Certain bacterial patterns specific to atopy are associated with vitamin D concentration in blood serum. In consequence of the study, we concluded that the gut microbiota and vitamin D may be systematically involved in modulating immune responses. Further research is needed to attain full comprehension of the mechanisms underlying these associations and to determine the most efficient interventions for the prevention and treatment of autoimmune conditions.

BACKGROUND. More than one hundred candidate genes have been associated with longevity, including APOE, FOXO1A, GF1, IGF1, INCR, TP53, etc. Despite extensive research, the precise molecular and genetic underpinnings remain elusive due to the low reproducibility of the findings. Moreover, most studies have focused on exomes and have neglected intergenic regulatory regions of DNA.AIM. To examine the genetic and molecular basis of longevity and create a prognostic model that assesses the chance of reaching the age of 90.MATERIALS AND METHODS. To study the genetic predictors of longevity, 10,157 people were recruited, including 3,066 long-living individuals (90+ years). The recruitment of long-living individuals was carried out jointly with the Russian Clinical Research Center for Gerontology; other participants have been included from the database of the Center for Strategic Planning and Management of Biomedical Health Risks” of the Federal Medical-Biological Agency. A comprehensive medical history was collected for all participants (including data on chronic conditions), and wholegenome sequencing of blood cell DNA was performed. When determining the healthy long-living individuals, we have utilized the machine learningbased calculator of aging phenotype previously developed by us [1].RESULTS. A genome-wide association study (GWAS) involving 3,066 longliving individuals (90+ years) and 7,091 people aged 18 to 75 years confirmed the known association of APOE gene variants with longevity. Additionally, we discovered new associations in the TMEM59, LRRC7, FHIT, CPLX1, DDX31, GRIN1, DHX32, CACNA1C, FBXO21 and UBBP4 genes. The obtained results helped construct a polygenic score, which assesses an individual chance of becoming a long-living individual (ROC AUC = 0.78). However, long-living individuals are a phenotypically heterogeneous group, so determining only the chance of living to 90 years may not be enough. The functional status at this age should also be addressed. The genomes of healthy long-living individuals were compared with the genomes of ailing long-living individuals and those of a healthy population sample. Healthy longevity is mediated by completely different molecular mechanisms than the broader phenotype, and is associated with the genes NAV1, SDK1, ARHGAP39 and ITGAE. Regulatory RNAs, particularly the antisense RNA to the mRNA of the IPO9 gene product, were shown to significantly affect healthy longevity.CONCLUSIONS. This study of the genetic basis of longevity has shown that there is no single mechanism that would be a single and key predictor for life expectancy. Longevity has been and remains a multifactorial phenomenon. However, this work confirmed the association of variants in the APOE gene with life expectancy in the Russian population, as well as detected many new polymorphisms associated with longevity. A polygenic scale was proposed that predicts the chance of reaching the age of longevity with an accuracy of over 78%. The important role of regulatory regions of the genome in the phenotype formation was specifically highlighted. Moreover, the achievement of healthy longevity turned out to be mediated by completely different molecular mechanisms than the broader phenotype, and is associated with the genes NAV1, SDK1, ARHGAP39, and ITGAE.

BACKGROUND. A trend toward demographic aging of the population is currently observed in most countries worldwide. More and more people are achieving longevity, both due to environmental factors and lifestyle, as well as to molecular genetic processes. Few large-scale studies have examined all factors contributing to longevity both in Russia and globally. Fewer of them have used a multi-omics approach, which could provide a better insight into the phenomenon of longevity by integrating genomic, epigenomic, transcriptomic and metagenomic data. AIM. To study the longevity phenomenon in the Russian Federation using a comprehensive analysis of lifestyle, environmental, socio-economic, clinical and laboratory factors, as well as molecular genetic factors.MATERIALS AND METHODS. The five-year joint longevity study conducted by the Center for Strategic Planning and the Russian Clinical Research Center for Gerontology has successfully collected one of the world’s largest repositories, containing a unique database of over 20,000 biological samples from 5,000 long-living individuals from 10 regions of the Russian Federation. Each participant undergoes a detailed medical history analysis, a comprehensive geriatric assessment, a wide range of laboratory tests, and molecular genetic testing.RESULTS. An integrated approach to the study of longevity enabled the determination of main aging phenotypes, as well as the environmental and lifestyle factors associated therewith. The longitudinal design of the study also allowed for the identification of factors related to all-cause mortality, including mortality from COVID-19. State-of-the-art sequencing provided an opportunity to examine the molecular genetic factors underlying both longevity (86 genetic variants passed the genome-wide significance threshold for longevity, 2 of which were located in the coding region in the APOE gene) and socially significant geriatric syndromes, such as cognitive impairment (19 genetic variants passed the genome-wide significance threshold, several of which were also located in the APOE gene). The results of the genome-wide association studies have been used in the development of a polygenic score model that enables to assess an early risk for cognitive impairment with 69% accuracy and the longevity probability with 78% accuracy. The results were validated on independent cohorts, as well as in vitro and in vivo models. In addition to the genetic data analysis, the epigenetics of longevity has also been studied. The epigenetic data obtained during the study have enabled the development of a biological age assessment tool with an accuracy of 95%, outperforming other comparable models.CONCLUSIONS. This comprehensive approach, considering both multi-omics and clinical data, could facilitate the development of highly accurate predictive models for aging-associated diseases and biological age assessment models. It provides a better insight into the fundamental mechanisms of longevity and promotes personalized geriatric medicine.

It is known that the intestinal microbiome plays an important role in many biological processes of the human body. However, all factors and mechanisms influencing changes in the composition of the intestinal microbiome are not fully understood. As the results of previous studies show, long-term food preferences play a significant role in modulating the composition of the intestinal microbiota. At the same time, all the mechanisms fully reflecting the peculiarities of the relationship of vitamins, trace elements, and the composition of the intestinal microbiota are not adequately characterized. Vitamins and trace elements have a bidirectional effect on the intestinal microbiota. On the one hand, they influence the composition of the microbiota, its representation, number, and diversity. On the other hand, the microbiota is involved in the metabolism of trace elements, including the synthesis of certain vitamins. In this review, we have tried to summarize the currently known information reflecting the relationship between the main microelements and the bacterial community of the gut. The review showed that some vitamins, with additional use, entering the colon modulate its microbiome, increase and maintain the bacterial diversity of the gut microbiota, which affects the amount of synthesized short-chain fatty acids. Several vitamins, such as vitamins A and D, can also affect intestinal immunity and its barrier functions.

Background. In many studies over the past decade, scientists have made a connection between the composition of gut microbiota and human health. A number of publications have shown that gut bacteria are involved in many metabolic and physiological processes of the organism. The composition of the gut microbiome is unique for each person and is formed under the influence of various factors associated with both the individual characteristics of the body and the characteristics of the environment. Different regional characteristics make it necessary for the body to adapt to certain conditions, including temperature fluctuations. Living in areas with low temperatures, such as the Arctic zone, dictates the need for increased energy consumption, which affects the composition of the gut microbiome. Methods. In our study, an extensive questionnaire was conducted among the participants, where many questions were included about the dietary preferences of the study participants, which allowed them us to further divide them into groups according to their diets. Stool samples were collected from participants from 3 groups: Arctic native, Arctic newcomer and the control group. The next step was the isolation of bacterial DNA and sequencing the 16S rRNA gene. The analysis of the results of the diversity of the intestinal microbiota was carried out both with and without taking into account the dietary preferences of the participants. Results. As a result of comparing the intestinal microbiota obtained from residents of the Arctic zone with the gut microbiota of residents of other regions with a milder climate, significant differences are found. These differences may be related to limited food resources and a reduction in the variety of food products characteristic of this Arctic region. t was also found that representatives of the bacterial families Christensenellaceae and Muribaculaceae dominated the control group, both with traditional nutrition and with a dairy-free diet in comparison with the Arctic groups. The control group was dominated by representatives of the Prevotellaceae, Enterobacteriaceae and Comamonadaceae families compared to the Arctic group (with a traditional diet). The results also show that the number of representatives of the families Desulfovibrionaceae (with traditional diet) and Enterobacteriaceae (with milk-free diet) is growing in the Arctic group. Conclusions. In the course of this work, bacterial families characteristic of people living in the Arc-tic zone of the Far Eastern region of the Russian Federation were identified. Poor diet, difficult climatic conditions, and problems with logistics and medical care can have a strong impact on the health of this population. The main type of diet for the inhabitants of the Arctic is the traditional type of diet. They consume a large number of low-cost products, obtainget animal protein from poultry and canned food, and also eat a small number of fresh vegetables and fruits. Such a diet is due to the social status of the study participants and the climatic and geographical features of the region (difficulties in agriculture). With such a diet, we observe a decrease in representatives of the Christensenellaceae, Muribaculaceae, Eubacteriaceae, and Prevotellaceae families and an increase in representatives of the Enterobacteriaceae and Desulfovibrionaceae families among Arctic residents. This imbalance in the futuremay cause, this population may to develop various diseases in the future, including chronic diseases such as obesity, intestinal dysbiosis, inflammatory bowel diseases, and type 2 diabetes.

Background. Currently, it is known that the gut microbiota plays an important role in the functioning of the immune system, and a rebalancing of the bacterial community can arouse complex immune reactions and lead to immune-mediated responses in an organism, in particular, the development of atopic dermatitis (AD). Cytokines and chemokines are regulators of the innate and adaptive immune response and represent the most important biomarkers of the immune system. It is known that changes in cytokine profiles are a hallmark of many diseases, including atopy. However, it remains unclear how the bacterial imbalance disrupts the function of the immune response in AD. Objectives. We attempted to determine the role of gut bacteria in modulating cytokine pathways and their role in atopic inflammation. Methods. We sequenced the 16S rRNA gene from 50 stool samples of children aged 3–12 years who had confirmed atopic dermatitis, and 50 samples from healthy children to serve as a control group. To evaluate the immune status, we conducted a multiplex immunofluorescence assay and measured the levels of 41 cytokines and chemokines in the serum of all participants. Results. To find out whether changes in the composition of the gut microbiota were significantly associated with changes in the level of inflammatory cytokines, a correlation was calculated between each pair of bacterial family and cytokine. In the AD group, 191 correlations were significant (Spearman’s correlation coefficient, p ≤ 0.05), 85 of which were positive and 106 which were negative. Conclusions. It has been demonstrated that intestinal dysbiosis is associated with alterations in cytokine profiles, specifically an increase in proinflammatory cytokine concentrations. This may indicate a systemic impact of these conditions, leading to an imbalance in the immune system’s response to the Th2 type. As a result, atopic conditions may develop. Additionally, a correlation between known AD biomarkers (IL-5, IL-8, IL-13, CCL22, IFN-γ, TNF-α) and alterations in the abundance of bacterial families (Pasteurellaceae, Barnesiellaceae, Eubacteriaceae) was observed.