Personalized Nutrition for Microbiota Correction and Metabolism Restore in Type 2 Diabetes Mellitus Patients.

Type 2 diabetes is one of the most common noncommunicable diseases in the world. Recent studies suggest a link between type 2 diabetes and microbiota, as well as the ability to treat and prevent it using personalized approaches to nutrition. In this work, we conducted clinical studies on the effects of a personalized diet on 56 female patients. Biochemical, physical, and immunological parameters were measured by standard methods on days 1 and 18 of the experiment. Gut and oral microbiota studies were performed in dynamics on days 1, 7, 11, and 18 using real-time polymerase chain reaction. With the help of the developed information system, a personalized diet was developed for each participant of the experiment. In the group of patients following personalized diets a statistically significant decreasing levels of glucose, thymol test, creatinine, very low-density lipoprotein, urea, secretory IgA, and tumour necrosis factor-α, and improvement in all physical parameters were observed. There was a statistically significant increase in uric acid, sodium, and magnesium. Statistically significant changes in gut microbiota were observed in Enterococcus faecalis, Escherichia coli (lac+, lac-), Lactobacillus spp., and Candida spp. Such microorganisms of oral microbiota as E. faecalis, Lactobacillus spp., Pseudomonas aeruginosa, and Candida spp. demonstrated statistically significant changes. All these changes indicate an improvement in the patients' condition in the experimental group compared to the control group. Our algorithm used for the development of personalized diets for patients with diabetes type 2 demonstrated clinical efficacy of its implementation.

Current Status and Future Therapeutic Options for Fecal Microbiota Transplantation.

The intestinal microbiota plays an important role in maintaining human health, and its alteration is now associated with the development of various gastrointestinal (ulcerative colitis, irritable bowel syndrome, constipation, etc.) and extraintestinal diseases, such as cancer, metabolic syndrome, neuropsychiatric diseases. In this context, it is not surprising that gut microbiota modification methods may constitute a therapy whose potential has not yet been fully investigated. In this regard, the most interesting method is thought to be fecal microbiota transplantation, which consists of the simultaneous replacement of the intestinal microbiota of a sick recipient with fecal material from a healthy donor. This review summarizes the most interesting findings on the application of fecal microbiota transplantation in gastrointestinal and extraintestinal pathologies.

Hypothesis of "stroke-stop" formula: a tool for risk index determination in development of acute cerebrovascular disease in asymptomatic individuals with carotid stenosis.

BACKGROUND: Extracranial carotid artery disease is considered a risk factor for developing acute cerebrovascular diseases. The paper suggests the "Stroke-Stop" formula as hypothesis for the determination of the risk of developing stroke in asymptomatic individuals with carotid stenosis. The formula is based on a mathematical calculation of the major risk factors for stroke: the degree of ICA (internal carotid artery) stenosis, the morphological structure of the atherosclerotic plaque and the level of lipoprotein-associated phospholipase A2 (Lp-PLA2) concentration. METHODS: The cross sectional study included 70 patients with atherosclerotic ICA stenosis. Among vascular inflammatory markers, Lp-PLA2 was determined with concentration 252.7-328.6 mg/l. The obtained results were evaluated using descriptive statistics (the frequency, percentage ratio) as well as the one-way analysis of variance (ANOVA) and chi-square test. RESULTS: The risk of stroke development is eminently increasing with the progression of ICA stenosis and elevation of Lp-PLA2 levels. In patients with echolucent plaque, the risk of stroke development was significantly higher in correlation with patients with echogenic plaque. Based on calculations using "Stroke-Stop" formula, three main groups were generated: low (< 70 points), medium (70-100 points) and high (> 100 points) risk of stroke development. CONCLUSIONS: Hypothesis of "Stroke-Stop" formula is proposed for better selection of patients who should be indicated for surgical treatment and will be evaluated in prospective study. In order to verify this hypothesis, we plan to do prospective study using "Stroke-Stop" formula for ipsilateral annual stroke rate in asymptomatic individuals with carotid stenosis who receive conservative therapy.

Lack of effect of bioactive-rich extracts of pomegranate, persimmon, nettle, dill, kale and Sideritis and isolated bioactives on platelet function.

BACKGROUND: The health benefits of fruit and vegetable-rich diets may be partly due to modulation of platelet activity by bioactive phytochemicals. The aim of this study was to investigate the effects of bioactive-rich plant extracts and isolated bioactive metabolites on platelet function. Blood samples (n =15 subjects) were treated with extracts of bioactive-rich plants consumed as traditional foods in the Black Sea region, or with human metabolites of the bioactives quercetin and sulforaphane. Platelet function was assessed using the PFA-100. RESULTS: None of the extracts containing various flavonoids, glucosinolates and other bioactives, or isolated bioactive metabolites of quercetin or sulforaphane, caused significant changes in PFA-100 closure time (CT). In contrast, the positive controls (aspirin and Abciximab) consistently caused significant increases in CT for the platelet agonists epinephrine and ADP, respectively. CONCLUSION: These data do not support the notion that these plant bioactives can improve human platelet function.

Bioactive-rich extracts of persimmon, but not nettle, Sideritis, dill or kale, increase eNOS activation and NO bioavailability and decrease endothelin-1 secretion by human vascular endothelial cells.

BACKGROUND: There is increasing evidence that consumption of plant bioactives such as polyphenols and glucosinolates reduces cardiovascular disease risk and improves endothelial function. In the Black Sea area, a number of plants are consumed alone and as ingredients in traditional foods, and dill, nettle, kale, Sideritis and persimmon were identified as bioactive-rich traditional food plants. The present study investigated the effects of plant extracts on cellular markers of endothelial function (eNOS activation and expression and ET-1 secretion). RESULTS: Treatment of human umbilical vein endothelial cells with persimmon extract significantly increased Akt and eNOS phosphorylation and nitric oxide metabolites and significantly decreased secretion of ET-1 to the media after 24 h compared with a vehicle control (all P < 0.01). None of the other plant extracts significantly altered any markers of endothelial function. CONCLUSION: These findings suggest that persimmon fruit contains bioactives that can improve endothelial function via activation of eNOS and reduction in ET-1 secretion, but that dill, kale, Sideritis and nettle do not.

Traditional foods from the Black Sea region as a potential source of minerals.

BACKGROUND: In the past few years, minerals have assumed great importance in public health. As a consequence, considerable research has been carried out to better understand their physiological role and the health consequences of mineral-deficient diets, to establish criteria for defining the degree of public health severity of malnutrition, and to develop prevention and control strategies. In most countries, there is limited information on the mineral content of traditional foods, and consequently it is very difficult to estimate mineral intake across these countries. RESULTS: Ten minerals were quantified in 33 traditional foods from Black Sea area countries. Our results indicate a considerable variability among the analysed traditional foods; nevertheless, the most abundant components were sodium (ranging from 40.0 to 619 mg 100 g(-1), for kvass southern and herbal dish, respectively), potassium (varied between 45.5 mg 100 g(-1) for millet ale and 938 mg 100 g(-1) for roasted sunflower seeds), and phosphorus (22.2 mg 100 g(-1) and 681 mg 100 g(-1) for sauerkraut and roasted sunflower seeds, respectively). CONCLUSION: This is the first study that provides validated data on the mineral content for 33 traditional foods from Black Sea area countries, which is important in order to elucidate their role in the dietary pattern of populations and to preserve and promote these foods.

New nutritional composition data on selected traditional foods consumed in Black Sea Area countries.

BACKGROUND: Traditional foods are an important part of the culture, history, identity and heritage of a region or country and are key elements in dietary patterns. In most countries there is limited information on the nutritional composition of such foods and therefore there is a need to investigate, register and promote traditional foods. One of the aims within the 'Sustainable exploitation of bioactive components from the Black Sea Area traditional foods' (BaSeFood) project is to generate for the first time new data on the nutritional composition of traditional foods from six Black Sea Area countries to promote their sustainable development and exploitation. RESULTS: Thirty-three traditional foods were analysed in an accredited laboratory to determine their nutritional composition, and the data were fully documented. The nutrient content varied widely because of the nature and variety of the analysed foods. The energy content ranged between 4 kcal per 100 g for kvass southern and 900 kcal per 100 g for mustard oil, with the exception of the analysed teas, which did not contribute to energy intake. CONCLUSION: The use of a common methodology for the study of traditional foods will enable countries to further investigate these foods. Moreover, a new nutritional knowledge base of traditional foods from Black Sea Area countries will contribute to promote local biodiversity and sustainable diets by maintaining healthy dietary patterns within local cultures.

Effects of bioactive-rich extracts of pomegranate, persimmon, nettle, dill, kale and Sideritis and isolated bioactives on arachidonic acid induced markers of platelet activation and aggregation.

BACKGROUND: The beneficial effect of fruit- and vegetable-rich diets on cardiovascular health is partly attributed to the effect of their bioactive compounds on platelet function. The aim of this study was to investigate the effects of bioactive-rich plant extracts and isolated bioactive metabolites on platelet function. Blood samples from healthy subjects (n = 4) and subjects with metabolic syndrome (n = 4) were treated with six extracts of bioactive-rich plants consumed as traditional foods in the Black Sea region, or with human metabolites of the bioactives quercetin and sulforaphane. Markers of arachidonic acid induced platelet activation and platelet-leucocyte aggregation were assessed using flow cytometry. RESULTS: In subjects with metabolic syndrome, kale extract significantly inhibited agonist induced P-selectin expression (P = 0.004). Sulforaphane-cysteine-glycine, a human plasma metabolite of the related glucosinolate, glucoraphanin, significantly inhibited P-selectin and GPIIb-IIIa expression (P = 0.020 and 0.024, respectively) and platelet-neutrophil aggregation (P = 0.027). Additionally, pomegranate extract significantly inhibited GPIIb-IIIa expression (P = 0.046) in subjects with metabolic syndrome. In healthy subjects only dill extract significantly inhibited agonist induced P-selectin expression (P = 0.025). CONCLUSION: These data show that bioactive-rich extracts of kale and pomegranate that are consumed as traditional plant foods of Black Sea area countries were effective in modulating platelet function.

Definition and documentation of traditional foods of the Black Sea Area Countries: potential nutrition claims.

BACKGROUND: Nutrition and health claims are permitted in foods marketed in the European Union under Regulation 1924/2006. Quality products such as traditional foods might benefit from this act, as it can highlight their nutritional richness. In this study the nutritional content of 33 traditional foods from the Black Sea Area Countries was evaluated against the thresholds of the Regulation for nutrition claims. RESULTS: Most of the foods were eligible to bear several nutrition claims, mostly related to their fat, sugar, fiber and sodium content. The average number of claims per traditional food was two, with a range between zero and nine. Overall, about 72 nutrition claims were potentially relevant for the 33 traditional foods studied. Foods linked with the most claims were nuts and seeds. CONCLUSION: The inclusion of traditional foods under this standardized European scheme could be an efficient way to highlight their possible beneficial nutritional properties. The production and marketing of traditional foods could be of benefit to both the health of consumers and the economic viability of producers, especially small- and medium-size enterprises.

Carotenoids, vitamins (A, B2, C and E) and total folate of traditional foods from Black Sea Area countries.

BACKGROUND: Carotenoids, vitamins (A, B2, C and E) and total folate are related to health promotion. However, there are still many food matrices for which the content of these compounds is not available. In order to fill this gap, traditional foods from Black Sea Area countries (BSAC) were analysed in order to investigate their potential health benefits. RESULTS: The most abundant carotenoid was ß-carotene. Plum jam was the sample with the highest ß-carotene content (608 µg 100 g(-1) edible portion). The group of vegetables and vegetable-based foods contributed most to ß-carotene content. Evergreen cherry laurel presented the highest l-ascorbic acid content (29.9 mg 100 g(-1) edible portion), while the highest riboflavin and total folate contents were found for roasted sunflower seeds. Approximately 61% of the analysed samples showed quantifiable amounts of α-tocopherol but did not contain retinol. CONCLUSION: Despite the great variability in the content of carotenoids, vitamins and total folate, most of the analysed traditional foods from BSAC can be considered good sources of these compounds. Therefore, owing to their putative health benefits, the consumption of those with higher contents of these compounds should be encouraged and promoted.

Synthesis, Biological Evaluation and Molecular Docking Studies of Novel Series of Bis-1,2,4-Triazoles as Thymidine Phosphorylase Inhibitor.

Introduction: Heterocyclic compounds have diverse biological activities and potential in drug development. This study aims to synthesize novel compounds with two 1,2,4-triazole cores and evaluate their biological properties, particularly their inhibitory activity against thymidine phosphorylase (TP), an enzyme involved in various physiological processes. Methods: The compounds were synthesized by reacting 5,5'-butane-bis-1,2,4-triazole derivatives with prenyl bromide. Characterization involved various techniques, including spectroscopy and elemental analysis. Antimicrobial potential was evaluated against bacteria and fungi, with comparative antibiotics as references. Inhibitory activity against TP was assessed, and molecular docking studies were conducted. Results: Six compounds were successfully synthesized and their structures confirmed. The synthesized triazole derivatives exhibited high biological activity, with compounds 2 and 6 showing the most promising TP inhibition. Molecular docking studies revealed interactions between compound 2 and TP, involving nine amino acids. Discussion: The synthesis of novel compounds with two 1,2,4-triazole cores contributes significantly to bis-triazole research. These compounds have potential as anti-tumor agents due to their inhibitory activity against TP, a crucial enzyme in tumor growth and metastasis. Comparative evaluation against antibiotics highlights their potency. Docking results provide insights into their interactions with TP, supporting their potential as potent TP inhibitors. Further research should focus on evaluating their efficacy in biological models, understanding their mechanisms of action, and optimizing their activities. Conclusion: The synthesized compounds with two 1,2,4-triazole cores exhibit significant biological activity, including strong TP inhibition and broad-spectrum antimicrobial effects. These findings emphasize their potential as anti-tumor agents and the need for further exploration and optimization. Future research should focus on evaluating their efficacy in biological models, understanding their mechanisms of action, and developing more potent bis-triazole derivatives for drug discovery efforts. The combined results from assays and docking studies support the therapeutic potential of these compounds as anti-tumor agents.

Biologically Active Substance Content in Edible Plants of Zakarpattia and Their Elemental Composition Model.

Consumption of edible plants satisfies a significant part of human body needs in macro- and micronutrients while biologically active substances contain strong antioxidant properties and reduce the risk of a number of diseases. Balanced nutrition and design of personalized diets and treatment rely on the data on the content of macro- and micronutrients and biologically active substances. We determined polyphenol and anthocyanin content in 22 species of local edible plants using modified spectrophotometric method with Folin-Ciocalteu reagent as well as chemical elements' content in a mixture of edible plants from 13 regions using standard procedures. We performed correlational analysis of the obtained data and analysis of the main components in OriginLab, developed regional models of chemical elements' content for a mixture of edible plants, and conducted cluster analysis using common tools in Python. The results of biologically active substances' study demonstrated that the highest content of polyphenolic compounds and anthocyanins was found in grape meal of Vitis vinifera L. The study of chemical elements' content demonstrated that edible plants from lowland areas are the best and revealed clear dependences of the elements on each other and geographical conditions. The analysis of the principal components confirmed this finding. Based on the obtained data, a number of regional models of chemical elements' content in a mixture of edible plants were built, tested, and evaluated. Obtained results are the basis for designing various diets, filling composite databases of the region's food, and creating the newest biologics-pharmabiotics.

Gut Microbiota Species Can Provoke both Inflammatory and Tolerogenic Immune Responses in Human Dendritic Cells Mediated by Retinoic Acid Receptor Alpha Ligation.

Dendritic cells are considered as the main coordinators of both mucosal and systemic immune responses, thus playing a determining role in shaping the outcome of effector cell responses. However, it is still uncovered how primary human monocyte-derived DC (moDC) populations drive the polarization of helper T (Th) cells in the presence of commensal bacteria harboring unique immunomodulatory properties. Furthermore, the individual members of the gut microbiota have the potential to modulate the outcome of immune responses and shape the immunogenicity of differentiating moDCs via the activation of retinoic acid receptor alpha (RARα). Here, we report that moDCs are able to mediate robust Th1 and Th17 responses upon stimulation by Escherichia coli Schaedler or Morganella morganii, while the probiotic Bacillus subtilis strain limits this effect. Moreover, physiological concentrations of all-trans retinoic acid (ATRA) are able to re-program the differentiation of moDCs resulting in altered gene expression profiles of the master transcription factors RARα and interferon regulatory factor 4, and concomitantly regulate the cell surface expression levels of CD1 proteins and also the mucosa-associated CD103 integrin to different directions. It was also demonstrated that the ATRA-conditioned moDCs exhibited enhanced pro-inflammatory cytokine secretion while reduced their co-stimulatory and antigen-presenting capacity thus reducing Th1 and presenting undetectable Th17 type responses against the tested microbiota strains. Importantly, these regulatory circuits could be prevented by the selective inhibition of RARα functionality. These results altogether demonstrate that selected commensal bacterial strains are able to drive strong effector immune responses by moDCs, while in the presence of ATRA, they support the development of both tolerogenic and inflammatory moDC in a RARα-dependent manner.

Probiotics and immunity: provisional role for personalized diets and disease prevention.

There is great interest in the interaction between diet and immune system and concomitantly in the potential of probiotic bacteria, especially given recent advances in understanding of gut microbiota effects on health in the context of microbiome research. Following our recent study on bacterial wall elasticity as a predictive measure of phagocytic cellular reactions and related outcomes, a question was raised regarding the scope of the application of these findings in various medical conditions in the context of predictive, preventive, and personalized medicine (PPPM). This summarizing review of the data describes the contributions, both observed and potential, of probiotics to the gut-brain axis and various medical conditions, including immune and atopic states, metabolic and inflammatory diseases-including liver disease and diabetes mellitus-cancer, and more. It also suggests novel insights for a number of beneficial applications of probiotics and advances in development of novel probiotic-based treatments and personalized diets, as well as application of sophisticated imaging techniques and nanobiotechnologies that can be adopted in the near future by innovative medical experts, warranting further research and practical translation.

The role of beneficial bacteria wall elasticity in regulating innate immune response.

BACKGROUND: Probiotics have great potential to contribute to development of healthy dietary regimes, preventive care, and an integrated approach to immunity-related disease management. The bacterial wall is a dynamic entity, depending on many components and playing an essential role in modulating immune response. The impact of cell wall elasticity on the beneficial effects of probiotic strains has not been sufficiently studied. The aim was to investigate the effect of lactic acid bacteria (LAB) and bifidobacteria strains on phagocytic system cells (macrophages) as related to bacterial wall elasticity, estimated using atomic force microscopy (AFM). METHODS: We conducted studies on Balb/c line mice 18-20 g in weight using lyophilized strains of LAB-Lactobacillus acidophilus IMV B-7279, Lactobacillus casei IMV B-7280, Lactobacillus delbrueckii subsp. bulgaricus IMV B-7281, and bifidobacteria-Bifidobacterium animalis VKL and Bifidobacterium animalis VKB. We cultivated the macrophages obtained from the peritoneal cavity of mice individually with the strains of LAB and bifidobacteria and evaluated their effect on macrophages, oxygen-dependent bactericidal activity, nitric oxide production, and immunoregulatory cytokines. We used AFM scanning to estimate bacterial cell wall elasticity. RESULTS: All strains had a stimulating effect on the functional activity of macrophages and ability to produce NO/NO2 in vitro. Lactobacilli strains increased the production of IL-12 and IFN-γ in vitro. The AFM demonstrated different cell wall elasticity levels in various strains of LAB and bifidobacteria. The rigidity of the cell walls among lactobacilli was distributed as follows: Lactobacillus acidophilus IMV B-7279 > Lactobacillus casei IMV B-7280 > Lactobacillus delbrueckii subsp. bulgaricus IMV B-7281; among the strains of bifidobacteria: B. animalis VKB > B. animalis VKL. Probiotic strain survival in the macrophages depended on the bacterial cell wall elasticity and on the time of their joint cultivation. CONCLUSION: LAB and bifidobacteria strains stimulate immune-modulatory cytokines and active oxygen and nitrogen oxide compound production in macrophages. Strains with a more elastic cell wall according to AFM data demonstrated higher resistance to intracellular digestion in macrophages and higher level of their activation. AFM might be considered as a fast and accurate method to assess parameters of probiotic strain cell wall to predict their immune-modulatory properties.