Argul Issilbayeva

The gut microbiome has been proposed as a contributor to Alzheimer’s disease (AD) pathogenesis via the microbiota–gut–brain axis, but findings across cohorts are inconsistent and scarce data exist from Central Asian populations. We used shotgun metagenomic sequencing to compare the gut microbiome of AD patients and cognitively healthy controls from Kazakhstan. In a cross-sectional case–control study (35 AD, 39 Control), we profiled taxonomic and functional (HUMAnN pathway) composition, and compared alpha/beta diversity, individual taxa and pathways, and their association with clinical and demographic variables (Mann–Whitney U test, PERMANOVA/PERMDISP, OLS regression, all BH-FDR corrected, sensitivity analysis using ANCOM-BC2), with sensitivity analyses adjusting for age and BMI and applying Bonferroni correction. Within the AD group, circulating adiponectin—measured only in this group—was examined for associations with microbiome features in an exploratory analysis. Alpha diversity was lower in AD (q < 0.05). Community composition also separated by group on PERMANOVA (R² = 8.6%, p = 0.001), and this separation held after adjusting for age and BMI. A total of 178 taxa differed significantly between groups (BH-FDR; 37 were also Bonferroni-significant), most prominently depletion of Faecalibacterium and enrichment of Eisenbergiella and Desulfovibrio in AD; 100 pathways differed significantly (20 Bonferroni-significant). Three clinical/demographic variables (total bilirubin, atherogenic index, BMI) were associated with specific taxa or pathways. Within the AD group, adiponectin correlated negatively with the pathway assimilatory sulfate reduction IV (rho = −0.60, q = 0.015). AD in this Central Asian cohort was associated with a less diverse, compositionally distinct gut microbiome, with depletion of butyrate-producing Firmicutes and enrichment of sulfate-reducing taxa, alongside other taxa whose direction of association differed from prior reports.

Background/Objectives: Cardiovascular diseases remain the leading cause of global mortality, with the gut microbiome emerging as a critical factor. This study aimed to characterize gut microbiome composition and metabolic pathways in individuals with low cardiovascular risk (LCR) compared to healthy controls to reveal insights into early disease shifts. Methods: We performed shotgun metagenomic sequencing on fecal samples from 25 LCR individuals and 25 matched healthy controls. Participants underwent a comprehensive cardiovascular evaluation. Taxonomic classification used MetaPhlAn 4, and functional profiling employed HUMAnN 3. Results: Despite similar alpha diversity, significant differences in bacterial community structure were observed between groups (PERMANOVA, p < 0.05). The LCR group showed enrichment of Faecalibacterium prausnitzii (p = 0.035), negatively correlating with atherogenic markers, including ApoB (r = −0.3, p = 0.025). Conversely, Fusicatenibacter saccharivorans positively correlated with ApoB (r = 0.4, p = 0.006). Metabolic pathway analysis revealed upregulation of nucleotide biosynthesis, glycolysis, and sugar degradation pathways in the LCR group, suggesting altered metabolic activity. Conclusions: We identified distinct gut microbiome signatures in LCR individuals that may represent early alterations associated with cardiovascular disease development. The opposing correlations between F. prausnitzii and F. saccharivorans with lipid parameters highlight their potential roles in cardiometabolic health. These findings suggest gut microbiome signatures may serve as indicators of early metabolic dysregulation preceding clinically significant cardiovascular disease.

Background. Atherosclerosis remains the leading cause of cardiovascular mortality worldwide. This review examines the emerging role of the gut microbiome in atherosclerosis pathogenesis. Recent advances in sequencing technologies have enabled deeper examination of complex interactions between intestinal microbial communities and cardiovascular health. Methods. This review followed MOOSE guidelines, searching PubMed, Scopus, Web of Science, and Embase databases through March 2024. Search terms included "gut microbiome," "atherosclerosis," and related concepts. Studies examining relationships between gut microbiome composition and AS were included, with data extracted using standardized forms and organized into four categories for qualitative synthesis. Results. Research reveals atherosclerosis patients exhibit reduced bacterial diversity and altered Firmicutes to Bacteroidetes ratios. Specific taxonomic signatures include increased Enterobacteriaceae and decreased butyrate-producing bacteria. Key microbial metabolites influence atherosclerosis development: short-chain fatty acids demonstrate anti-inflammatory properties; trimethylamine-N-oxide enhances macrophage cholesterol accumulation; bile acids modulate lipid metabolism; and lipopolysaccharides trigger inflammatory cascades involved in plaque formation. Conclusion. Understanding gut microbiome contributions to atherosclerosis pathogenesis offers new possibilities for prevention and treatment through microbiota modulation or targeting specific microbial metabolites, representing a paradigm shift toward personalized approaches considering interactions between genetics, environment, and microbiome.

Introduction: This study investigates the effects of polyphenol supplementation on gut microbiome composition and cardiovascular health in patients with ST-segment elevation myocardial infarction (STEMI).Methods: Double-blind randomized control trial where participants received either polyphenol supplementation or placebo for 3 months, after which composition of the gut microbiome; clinical and laboratory parameters, including TMAO levels and oxidative stress levels, were assessed.Results: The stable TMAO levels (from 0.5 [0.2–0.9] to 0.4 [0.3–0.9] μmol, p > 0.05) were observed in the polyphenol group, compared to the increase observed in the placebo group (from 0.5 [0.3–0.6] to 0.7 [0.5–1.4] μmol, p < 0.001). Polyphenol supplementation significantly decreased the Firmicutes/Bacteroidetes ratio (p = 0.04) and increased beneficial bacteria such as Roseburia (p = 0.01), Agathobaculum sp. (p = 0.004), Alistipes finegoldii (p = 0.04) and Sellimonas (p = 0.002). Predicted metabolic pathways analysis supports potential mechanisms linking polyphenol intake to microbiome modulation and TMAO regulation.Conclusion: Our findings demonstrate that polyphenol supplementation maintains stable TMAO levels by restructuring gut microbiome composition in STEMI patients, evidenced by a more focused microbiome with a significant increase in beneficial butyrate-producing bacteria (Roseburia, Agathobaculum sp., Alistipes finegoldii, and Sellimonas) and a decreased Firmicutes/Bacteroidetes ratio, suggesting microbiome-mediated cardioprotective effects. While promising,l our preliminary findings require further studies with larger cohorts and more advanced sequencing methods to establish their significance for cardiovascular health.Clinical trial registration: ClinicalTrial.gov, identfier: NCT06573892.

Growing evidence supports a bidirectional relationship between the gut microbiome and mental health. This study investigated the association between gut microbiota, depression, and suicidal behavior by analyzing fecal samples from 35 individuals with varying depression levels and 36 completed suicide cases. Standardized psychometric assessments were used for depression evaluation. Analysis revealed significant taxonomic differences between groups, with increased abundance of Firmicutes, Clostridia, Lachnospiraceae, Blautia, and Dorea in suicide cases, which also positively correlated with depression severity. Metabolic pathway analysis demonstrated a notable dichotomy: suicide cases showed elevated pathways related to infection processes, inflammation, and antibiotic resistance, while the control group exhibited higher energy metabolism and vitamin synthesis pathways. The findings establish specific microbiome profiles associated with both depression symptoms and suicidal behavior, suggesting that gut dysbiosis may influence mental health through altered energy metabolism and inflammatory processes, potentially offering new perspectives for diagnostic and therapeutic approaches.

Short-chain fatty acids (SCFAs), produced through fermentation of dietary fibers by gut bacteria, play a central role in modulating cardiovascular function and heart failure (HF) development. The progression of HF is influenced by intestinal barrier dysfunction and microbial translocation, where SCFAs serve as key mediators in the gut–heart axis. This review examines the complex metabolic interactions between SCFAs and other gut microbiota metabolites in HF, including their relationships with trimethylamine N-oxide (TMAO), aromatic amino acids (AAAs), B vitamins, and bile acids (BAs). We analyze the associations between SCFA production and clinical parameters of HF, such as left ventricular ejection fraction (LVEF), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and glomerular filtration rate (GFR). Gaining insights into metabolic networks offers new potential therapeutic targets and prognostic markers for managing heart failure, although their clinical significance needs further exploration.

Objective The oral microbiome is one of the most complex microbial ecosystems in the host. This study aimed to investigate and characterize the oral microbiome composition in Kazakhstani adolescents associated with dental caries. Methodology The study included 312 adolescents, with 241 individuals presenting with caries and 71 caries-free, aged 12-15 years. Dental caries assessment was performed using DMFT (Decayed, missed, filled teeth) index. Oral samples were collected, and 16S rRNA (16S ribosomal ribonucleic acid) gene sequencing targeting the V3-V4 hypervariable regions on an Illumina MiSeq platform was performed to profile the microbial communities. Functional metagenomic predictions were generated using PICRUSt2 v2.5.0, using the KEGG database for bacterial pathway abundance estimation. Data analysis was conducted using Python 3.9.16 and R 4.2.2. Results The alpha diversity was insignificant, while beta diversity analysis demonstrated clear distinctions by Bray-Curtis (F=2.5, p=0.003) and weighted UniFrac distances (F=4.4, p=0.002). The Neisseria and Prevotella genera, and Gammaproteobacteria class showed significant associations with dental caries (MaAsLin2 p≤0.05, LDA≥2), stronger predictive power (AUC=0.65, F1=0.83), and higher predicted functional activity through glutathione metabolism, RNA degradation, and unsaturated fatty acid metabolism pathways. Conclusions This study identified specific oral microbiome patterns associated with dental caries in Kazakhstani adolescents, revealing interactions between key bacterial taxa and metabolic pathways.

Objective: The primary objective is to study the impact of gut microbiota and their interactions with diverse immunological markers on the development of rheumatoid arthritis. Methods: This study was performed in Astana, Kazakhstan, and included 77 Kazakh female patients older than 18 years, who met the American College of Rheumatology 2010 classification criteria for rheumatoid arthritis (RA), and 113 healthy controls. The DNA was extracted from fecal samples obtained from all study participants for subsequent sequencing at the 16S rRNA gene V1-V3 locus, facilitating the analysis of the gut microbiome. The Multiplex immunoassay was employed to measure the concentrations of inflammatory cytokines, chemokines, and immunoglobulins in both fecal and plasma samples. Results: Our taxonomic analysis revealed significant differences in the composition of the gut microbiota between the healthy control cohort and the cohort with rheumatoid arthritis RA. Alpha diversity was significantly lower in the RA group. Lachnospiraceae were the most abundant taxon and found to be crucial, showing correlations with immunological markers such as IL5. Additionally, Lachnospiraceae and Oscillospiraceae exhibited the most predictable power and distinguished the composition of both study groups. Conclusion: Our study identifies key differences in the gut microbiome of RA patients, revealing distinct microbial patterns and specific taxa abundance. We highlight potential biomarkers in immunological and bacterial pathways, offering insights into RA development and indicating possibilities for personalized treatment.

Introduction: Dietary habits and eating patterns of individuals have a significant impact on overall health. Proper nutrition is vital to preventing chronic diseases and improving physical and mental performance. Kazakhstan, a rapidly developing country in Central Asia, offers a unique opportunity to study the diverse dietary behavior of its population due to cultural, ethnic and geographic differences. Purpose: to study dietary habits and nutritional status of persons aged 18 years and older in various regions of Kazakhstan. Materials and methods: The study was conducted over a period of six months and covered urban and rural areas of various regions of Kazakhstan, including large cities such as Astana, Almaty and Aktobe, as well as their surrounding rural areas. A stratified sample of 370 participants was used and were randomly selected from each stratum to ensure representativeness. Statistical analyzes included determination of dietary patterns, assessment of agreement between food frequency questionnaires and 24-hour recalls, and correlation and visualization of agreement between these methods using Bland-Altman plots. To improve the accuracy of food intake estimates, Willett energy adjustment was applied using Python 3.9 and associated libraries (NumPy, SciPy, pandas, Scikit-learn). Results: In this study, conducted in different regions of Kazakhstan, significant regional differences in food intake and nutritional status were observed among 370 participants. A comparative analysis of food frequency questionnaires (FFQ) and 24-hour recall showed that urban residents tend to have higher consumption of processed foods, whereas rural residents are more likely to consume traditional, minimally processed foods. This difference highlights the influence of geography, culture, and economic factors on eating habits. Urban and rural settings exhibited unique dietary patterns: urban areas experienced greater diversity in food consumption, but also a higher propensity for nutrient inequalities. Conclusions: Combining multiple dietary assessment tools and using larger sample sizes may improve the accuracy and reliability of dietary data. Additionally, education and training of participants in portion size estimation and dietary reporting may help improve the quality of data collected using these methods. In conclusion, the study shows that the FFQ and 24-hour recall methods are reliable and correlate well in assessing intake of essential nutrients in Kazakhstan. Введение: Диетические привычки и режим питания людей существенно влияют на общее состояние здоровья. Правильное питание имеет жизненно важное значение для предотвращения хронических заболеваний и повышения физической и умственной работоспособности. Казахстан, быстро развивающаяся страна в Центральной Азии, предлагает уникальную возможность изучить разнообразное пищевое поведение своего населения, обусловленное культурными, этническими и географическими различиями. Цель: изучить особенности питания и статус питания у лиц в возрасте 18 лет и старше в различных регионах Казахстана. Материалы и методы: Исследование проводилось в течение шести месяцев и охватывало городские и сельские районы различных регионов Казахстана, включая крупные города, такие как Астана, Алматы и Актобе, а также прилегающие к ним сельские районы. Была использована стратифицированная выборка из 370 участников, которые были случайным образом выбраны из каждой страты, чтобы обеспечить репрезентативность. Статистический анализ включал определение структуры пищевого рациона, оценку соответствия между анкетами по частоте приема пищи и 24-часовыми отзывами, а также корреляцию и визуализацию согласия между этими методами с использованием графиков Бланда-Альтмана. Для повышения точности оценок потребления пищи применялась энергетическая корректировка Уиллетта с использованием Python 3.9 и соответствующих библиотек (NumPy, SciPy, pandas, Scikit-learn). Результаты: В этом исследовании, проведенном в различных регионах Казахстана, среди 370 участников наблюдались значительные региональные различия в потреблении пищи и статусе питания. Сравнительный анализ опросников частоты питания (FFQ) и 24-часовых воспоминаний показал, что жители городов имеют тенденцию к более высокому потреблению обработанных пищевых продуктов, тогда как жители сельской местности чаще потребляют традиционные, минимально обработанные продукты. Это...