Вчені України — лауреати міжнародних премій і нагород

Рецензія на книгу: Абліцов В.Г. «Вчені України — лауреати міжнародних премій і нагород» (Серія «Наука України у світовому інформаційному просторі». Вип. 4) Київ: Академперіодика, 2011. — 192 с

Responses of the gut microbiota to supplementary iron: a survey at the host-microbial interface

Contains fulltext : 132635.pdf (publisher's version ) (Open Access)Iron is a highly abundant metal on earth and is vital for virtually all organisms, including most bacterial species. Nonetheless, iron deficiency is the most prevalent human nutrition disorder worldwide, which can generally be treated by oral iron administration. However, oral iron administration in infection endemic regions is associated with an increased susceptibility of children to infections. The aim of this thesis was to investigate the impact of oral iron administration at the intestinal epithelial interface on i) the pathogenicity of intestinal pathogens, ii) the gut microbiota composition, iii) gut microbial metabolism, and iv) host responses. This thesis exemplifies that oral administration can increase the abundance of intestinal pathogens and may increase their pathogenicity, while it can decrease the abundance of beneficial gut microbes. Furthermore, it may also decrease host intestinal defenses (i.e. via: iron-induced oxidative damage to the gut wall, increased production of toxic microbial metabolites affecting the gut wall, or a decreased host innate defense) at the same time. This undesired combination may provide intestinal pathogens with increased opportunities to evade the host defense during oral iron therapy. Together this strengthens the idea that oral iron administration programs in developing countries with high infection pressure need to be set up with the highest amount of care, and should be accompanied with close health monitoring until the remaining questions about the actual effect of iron at the intestinal host-microbiota interface have been unraveled. Future research should also be directed at finding iron formulations that minimize the negative impact on the gut microbiome. This thesis exposes health problems and potential threats with regarding to oral iron administration and it increases the understanding of iron-driven alterations of host-pathogen interactions, which is indispensible in the design of safe iron formulations.Radboud Universiteit Nijmegen, 16 december 2014Promotor : Swinkels, D.W. Co-promotor : Tjalsma, H

Oral iron supplementation: Potential implications for the gut microbiome and metabolome in patients with CKD

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Iron-induced virulence of Salmonella enterica serovar typhimurium at the intestinal epithelial interface can be suppressed by carvacrol

Contains fulltext : 138357.pdf (publisher's version ) (Open Access)Oral iron therapy can increase the abundance of bacterial pathogens, e.g., Salmonella spp., in the large intestine of African children. Carvacrol is a natural compound with antimicrobial activity against various intestinal bacterial pathogens, among which is the highly prevalent Salmonella enterica serovar Typhimurium. This study aimed to explore a presumed interaction between carvacrol and bacterial iron handling and to assess the potential of carvacrol in preventing the increase of bacterial pathogenicity during high iron availability. S. Typhimurium was cultured with increasing concentrations of iron and carvacrol to study the effects of these combined interventions on growth, adhesion to intestinal epithelial cells, and iron uptake/influx in both bacterial and epithelial cells. In addition, the ability of carvacrol to remove iron from the high-affinity ligand transferrin and an Fe-dye complex was examined. Carvacrol retarded growth of S. Typhimurium at all iron conditions. Furthermore, iron-induced epithelial adhesion was effectively reduced by carvacrol at high iron concentrations. The reduction of growth and virulence by carvacrol was not paralleled by a change in iron uptake or influx into S. Typhimurium. In contrast, bioavailability of iron for epithelial cells was moderately decreased under these conditions. Further, carvacrol was shown to lack the properties of an iron binding molecule; however, it was able to weaken iron-ligand interactions by which it may possibly interfere with bacterial virulence. In conclusion, our in vitro data suggest that carvacrol has the potential to serve as a novel dietary supplement to prevent pathogenic overgrowth and colonization in the large intestine during oral iron therapy

Nutritional iron turned inside out: intestinal stress from a gut microbial perspective.

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Iron status and systemic inflammation, but not gut inflammation, strongly predict gender-specific concentrations of serum hepcidin in infants in rural kenya

Contains fulltext : 118695.pdf (publisher's version ) (Open Access)Hepcidin regulation by competing stimuli such as infection and iron deficiency has not been studied in infants and it's yet unknown whether hepcidin regulatory pathways are fully functional in infants. In this cross-sectional study including 339 Kenyan infants aged 6.0+/-1.1 months (mean+/-SD), we assessed serum hepcidin-25, biomarkers of iron status and inflammation, and fecal calprotectin. Prevalence of inflammation, anemia, and iron deficiency was 31%, 71%, 26%, respectively. Geometric mean (+/-SD) serum hepcidin was 6.0 (+/-3.4) ng/mL, and was significantly lower in males than females. Inflammation (C-reactive protein and interleukin-6) and iron status (serum ferritin, zinc protoporphyrin and soluble transferrin receptor) were significant predictors of serum hepcidin, explaining nearly 60% of its variance. There were small, but significant differences in serum hepcidin comparing iron deficient anemic (IDA) infants without inflammation to iron-deficient anemic infants with inflammation (1.2 (+/-4.9) vs. 3.4 (+/-4.9) ng/mL; P<0.001). Fecal calprotectin correlated with blood/mucus in the stool but not with hepcidin. Similarly, the gut-linked cytokines IL-12 and IL-17 did not correlate with hepcidin. We conclude that hepcidin regulatory pathways are already functional in infancy, but serum hepcidin alone may not clearly discriminate between iron-deficient anemic infants with and without infection. We propose gender-specific reference values for serum hepcidin in iron-replete infants without inflammation

Preservation of bacterial DNA in 10-year-old guaiac FOBT cards and FIT tubes

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Bacterial responses to a simulated colon tumor microenvironment

Item does not contain fulltextOne of the few bacteria that have been consistently linked to colorectal cancer (CRC) is the opportunistic pathogen Streptococcus gallolyticus. Infections with this bacterium are generally regarded as an indicator for colonic malignancy, while the carriage rate of this bacterium in the healthy large intestine is relatively low. We speculated that the physiological changes accompanying the development of CRC might favor the colonization of this bacterium. To investigate whether colon tumor cells can support the survival of S. gallolyticus, this bacterium was grown in spent medium of malignant colonocytes to simulate the altered metabolic conditions in the CRC microenvironment. These in vitro simulations indicated that S. gallolyticus had a significant growth advantage in these spent media, which was not observed for other intestinal bacteria. Under these conditions, bacterial responses were profiled by proteome analysis and metabolic shifts were analyzed by (1)H-NMR-spectroscopy. In silico pathway analysis of the differentially expressed proteins and metabolite analysis indicated that this advantage resulted from the increased utilization of glucose, glucose derivates, and alanine. Together, these data suggest that tumor cell metabolites facilitate the survival of S. gallolyticus, favoring its local outgrowth and providing a possible explanation for the specific association of S. gallolyticus with colonic malignancy

Diurnal Rhythm rather than Dietary Iron Mediates Daily Hepcidin Variations

Item does not contain fulltextBACKGROUND: The iron-regulating hormone hepcidin is a promising biomarker in the diagnosis of iron disorders. Concentrations of hepcidin have been shown to increase during the day in individuals who are following a regular diet. It is currently unknown whether these increases are determined by an innate rhythm or by other factors. We aimed to assess the effect of dietary iron on hepcidin concentrations during the day. METHODS: Within a 7-day interval, 32 volunteers received an iron-deficient diet on 1 day and the same diet supplemented with 65 mg ferrous fumarate at 0815 and 1145 on another day. Blood was drawn to assess ferritin, hepcidin-25, and transferrin saturation (TS) throughout both days at 4 time points between 0800 (fasted) and 1600. A linear mixed model for repeated data was used to analyze the effect of iron intake on TS and hepcidin concentrations. RESULTS: Baseline values of hepcidin at 0800 correlated significantly with ferritin (r = 0.61). During the day of an iron-deficient diet the mean TS was similar both in men and in women, whereas hepcidin increased. During the day with iron supplementation the mean TS was significantly higher both in men and in women, and the mean hepcidin was moderately but significantly higher in women (1.0 nmol/L, 95% CI, 0.2-1.8) but not in men (0.0 nmol/L, 95% CI, -0.8 to 0.8). CONCLUSIONS: Our data demonstrate that ferritin sets the basal hepcidin concentrations and suggest that innate diurnal rhythm rather than dietary iron mediates the daily hepcidin variations. These findings will be useful for optimizing sampling protocols and will facilitate the interpretation of hepcidin as an iron biomarker

Low gut microbiota diversity and dietary magnesium intake are associated with the development of PPI-induced hypomagnesemia.

Contains fulltext : 208665.pdf (publisher's version ) (Closed access)Proton pump inhibitors (PPIs) are used by millions of patients for the treatment of stomach acid-reflux diseases. Although PPIs are generally considered safe, about 13% of the users develop hypomagnesemia. Despite rising attention for this issue, the underlying mechanism is still unknown. Here, we examine whether the gut microbiome is involved in the development of PPI-induced hypomagnesemia in wild-type C57BL/6J mice. After 4 wk of treatment under normal or low dietary Mg(2+) availability, omeprazole significantly reduced serum Mg(2+) levels only in mice on a low-Mg(2+) diet without affecting the mRNA expression of colonic or renal Mg(2+) transporters. Overall, 16S rRNA gene sequencing revealed a lower gut microbial diversity in omeprazole-treated mice. Omeprazole induced a shift in microbial composition, which was associated with a 3- and 2-fold increase in the abundance of Lactobacillus and Bifidobacterium, respectively. To examine the metabolic consequences of these microbial alterations, the colonic composition of organic acids was evaluated. Low dietary Mg(2+) intake, independent of omeprazole treatment, resulted in a 10-fold increase in formate levels. Together, these results imply that both omeprazole treatment and low dietary Mg(2+) intake disturb the gut internal milieu and may pose a risk for the malabsorption of Mg(2+) in the colon.-Gommers, L. M. M., Ederveen, T. H. A., van der Wijst, J., Overmars-Bos, C., Kortman, G. A. M., Boekhorst, J., Bindels, R. J. M., de Baaij, J. H. F., Hoenderop, J. G. J. Low gut microbiota diversity and dietary magnesium intake are associated with the development of PPI-induced hypomagnesemia