Daily rhythms in gene expression of the human parasite Schistosoma mansoni.

BACKGROUND: The consequences of the earth's daily rotation have led to 24-h biological rhythms in most organisms. Even some parasites are known to have daily rhythms, which, when in synchrony with host rhythms, can optimise their fitness. Understanding these rhythms may enable the development of control strategies that take advantage of rhythmic vulnerabilities. Recent work on protozoan parasites has revealed 24-h rhythms in gene expression, drug sensitivity and the presence of an intrinsic circadian clock; however, similar studies on metazoan parasites are lacking. To address this, we investigated if a metazoan parasite has daily molecular oscillations, whether they reveal how these longer-lived organisms can survive host daily cycles over a lifespan of many years and if animal circadian clock genes are present and rhythmic. We addressed these questions using the human blood fluke Schistosoma mansoni that lives in the vasculature for decades and causes the tropical disease schistosomiasis. RESULTS: Using round-the-clock transcriptomics of male and female adult worms collected from experimentally infected mice, we discovered that ~ 2% of its genes followed a daily pattern of expression. Rhythmic processes included a stress response during the host's active phase and a 'peak in metabolic activity' during the host's resting phase. Transcriptional profiles in the female reproductive system were mirrored by daily patterns in egg laying (eggs are the main drivers of the host pathology). Genes cycling with the highest amplitudes include predicted drug targets and a vaccine candidate. These 24-h rhythms may be driven by host rhythms and/or generated by a circadian clock; however, orthologs of core clock genes are missing and secondary clock genes show no 24-h rhythmicity. CONCLUSIONS: There are daily rhythms in the transcriptomes of adult S. mansoni, but they appear less pronounced than in other organisms. The rhythms reveal temporally compartmentalised internal processes and host interactions relevant to within-host survival and between-host transmission. Our findings suggest that if these daily rhythms are generated by an intrinsic circadian clock then the oscillatory mechanism must be distinct from that in other animals. We have shown which transcripts oscillate at this temporal scale and this will benefit the development and delivery of treatments against schistosomiasis.

Are Pregnant Women Who Are Living with Overweight or Obesity at Greater Risk of Developing Iron Deficiency/Anaemia?

Low-grade inflammation is often present in people living with obesity. Inflammation can impact iron uptake and metabolism through elevation of hepcidin levels. Obesity is a major public health issue globally, with pregnant women often affected by the condition. Maternal obesity is associated with increased pregnancy risks including iron deficiency (ID) and iron-deficiency anaemia (IDA)-conditions already highly prevalent in pregnant women and their newborns. This comprehensive review assesses whether the inflammatory state induced by obesity could contribute to an increased incidence of ID/IDA in pregnant women and their children. We discuss the challenges in accurate measurement of iron status in the presence of inflammation, and available iron repletion strategies and their effectiveness in pregnant women living with obesity. We suggest that pre-pregnancy obesity and overweight/obese pregnancies carry a greater risk of ID/IDA for the mother during pregnancy and postpartum period, as well as for the baby. We propose iron status and weight gain during pregnancy should be monitored more closely in women who are living with overweight or obesity.

Iron status in the elderly: A review of recent evidence.

A comprehensive literature review of iron status in the elderly was undertaken in order to update a previous review (Fairweather-Tait et al, 2014); 138 summarised papers describe research on the magnitude of the problem, aetiology and age-related physiological changes that may affect iron status, novel strategies for assessing iron status with concurrent health conditions, hepcidin, lifestyle factors, iron supplements, iron status and health outcomes (bone mineral density, frailty, inflammatory bowel disease, kidney failure, cancer, cardiovascular, and neurodegenerative diseases). Each section of this review concludes with key points from the relevant papers. The overall findings were that disturbed iron metabolism plays a major role in a large number of conditions associated with old age. Correction of iron deficiency/overload may improve disease prognosis, but diagnosis of iron deficiency requires appropriate cut-offs for biomarkers of iron status in elderly men and women to be agreed. Iron deficiency (with or without anemia), anemia of inflammation, and anemia of chronic disease are all widespread in the elderly and, once identified, should be investigated further as they are often indicative of underlying disease. Management options should be reviewed and updated, and novel therapies, which show potential for treating anemia of inflammation or chronic disease, should be considered.

In Vitro Iron Bioavailability of Brazilian Food-Based by-Products.

Background: Iron deficiency is a public health problem in many low- and middle-income countries. Introduction of agro-industrial food by-products, as additional source of nutrients, could help alleviate this micronutrient deficiency, provide alternative sources of nutrients and calories in developed countries, and be a partial solution for disposal of agro-industry by-products. Methods: The aim of this study was to determine iron bioavailability of 5 by-products from Brazilian agro-industry (peels from cucumber, pumpkin, and jackfruit, cupuaçu seed peel, and rice bran), using the in vitro digestion/ Caco-2 cell model; with Caco-2 cell ferritin formation as a surrogate marker of iron bioavailability. Total and dialyzable Fe, macronutrients, the concentrations of iron-uptake inhibitors (phytic acid, tannins, fiber) and their correlation with iron bioavailability were also evaluated. Results: The iron content of all by-products was high, but the concentration of iron and predicted bioavailability were not related. Rice bran and cupuaçu seed peel had the highest amount of phytic acid and tannins, and lowest iron bioavailability. Cucumber peels alone, and with added extrinsic Fe, and pumpkin peels with extrinsic added iron, had the highest iron bioavailability. Conclusion: The results suggest that cucumber and pumpkin peel could be valuable alternative sources of bioavailable Fe to reduce iron deficiency in at-risk populations.

Alginate inhibits iron absorption from ferrous gluconate in a randomized controlled trial and reduces iron uptake into Caco-2 cells.

UNLABELLED: Previous in vitro results indicated that alginate beads might be a useful vehicle for food iron fortification. A human study was undertaken to test the hypothesis that alginate enhances iron absorption. A randomised, single blinded, cross-over trial was carried out in which iron absorption was measured from serum iron appearance after a test meal. Overnight-fasted volunteers (n = 15) were given a test meal of 200 g cola-flavoured jelly plus 21 mg iron as ferrous gluconate, either in alginate beads mixed into the jelly or in a capsule. Iron absorption was lower from the alginate beads than from ferrous gluconate (8.5% and 12.6% respectively, p = 0.003). Sub-group B (n = 9) consumed the test meals together with 600 mg calcium to determine whether alginate modified the inhibitory effect of calcium. Calcium reduced iron absorption from ferrous gluconate by 51%, from 11.5% to 5.6% (p = 0.014), and from alginate beads by 37%, from 8.3% to 5.2% (p = 0.009). In vitro studies using Caco-2 cells were designed to explore the reasons for the difference between the previous in vitro findings and the human study; confirmed the inhibitory effect of alginate. Beads similar to those used in the human study were subjected to simulated gastrointestinal digestion, with and without cola jelly, and the digestate applied to Caco-2 cells. Both alginate and cola jelly significantly reduced iron uptake into the cells, by 34% (p = 0.009) and 35% (p = 0.003) respectively. The combination of cola jelly and calcium produced a very low ferritin response, 16.5% (p < 0.001) of that observed with ferrous gluconate alone. The results of these studies demonstrate that alginate beads are not a useful delivery system for soluble salts of iron for the purpose of food fortification. TRIAL REGISTRATION: ClinicalTrials.gov NCT01528644.

Iron bioavailability in two commercial cultivars of wheat: comparison between wholegrain and white flour and the effects of nicotianamine and 2'-deoxymugineic acid on iron uptake into Caco-2 cells.

Iron bioavailability in unleavened white and wholegrain bread made from two commercial wheat varieties was assessed by measuring ferritin production in Caco-2 cells. The breads were subjected to simulated gastrointestinal digestion and the digests applied to the Caco-2 cells. Although Riband grain contained a lower iron concentration than Rialto, iron bioavailability was higher. No iron was taken up by the cells from white bread made from Rialto flour or from wholegrain bread from either variety, but Riband white bread produced a small ferritin response. The results probably relate to differences in phytate content of the breads, although iron in soluble monoferric phytate was demonstrated to be bioavailable in the cell model. Nicotianamine, an iron chelator in plants involved in iron transport, was a more potent enhancer of iron uptake into Caco-2 cells than ascorbic acid or 2'-deoxymugineic acid, another metal chelator present in plants.

Iron status in the elderly.

Iron deficiency anaemia is prevalent in older age, particularly after the age of 80. Serum ferritin concentrations also decline, although there is no evidence to suggest that changes in iron stores are an inevitable consequence of ageing. Chronic inflammation is a common condition in older people, making the measurement of iron status difficult, and it is likely that elevated levels of circulating hepcidin are responsible for changes in iron metabolism that result in systemic iron depletion. Other contributory factors are poor diet and some medications, such as aspirin. Anaemia in older age has undesirable health outcomes, including increased susceptibility to falling and depression. However, there are concerns about possible adverse effects of iron supplements, either in relation to pro-inflammatory effects in the gut or inappropriate tissue iron deposition. Brain iron levels are increased with age-related degenerative diseases, but it is not known if this is the cause or a consequence of the disease, and genetic factors are likely to play a role. In order to maintain body iron within the normal range a personalised approach is required, taking into account all of the factors that may affect iron metabolism and the available strategies for preventing iron deficiency or overload.

The contribution of diet and genotype to iron status in women: a classical twin study.

This is the first published report examining the combined effect of diet and genotype on body iron content using a classical twin study design. The aim of this study was to determine the relative contribution of genetic and environmental factors in determining iron status. The population was comprised of 200 BMI- and age-matched pairs of MZ and DZ healthy twins, characterised for habitual diet and 15 iron-related candidate genetic markers. Variance components analysis demonstrated that the heritability of serum ferritin (SF) and soluble transferrin receptor was 44% and 54% respectively. Measured single nucleotide polymorphisms explained 5% and selected dietary factors 6% of the variance in iron status; there was a negative association between calcium intake and body iron (p = 0.02) and SF (p = 0.04).

A high prevalence of zinc- but not iron-deficiency among women in rural Malawi: a cross-sectional study.

BACKGROUND: Zinc deficiency is often associated with nutritional iron deficiency (ID), and may be exacerbated by low selenium status. AIM: To investigate risk of iron and zinc deficiency in women with contrasting selenium status. METHODS: In a cross-sectional study, 1-day diet composites and blood samples were collected from self-selected Malawian women aged 18-50 years from low- (Zombwe) (n=60) and high-plant-available soil selenium (Mikalango) (n=60) districts. Diets were analyzed for trace elements and blood for biomarkers. RESULTS: Zinc deficiency (>90 %) was greater than ID anemia (6 %), or ID (5 %), attributed to diets low in zinc (median 5.7 mg/day) with high phytate:zinc molar ratios (20.0), but high in iron (21.0 mg/day) from soil contaminant iron. Zombwe compared to Mikalango women had lower (p<0.05) intakes of selenium (6.5 vs. 55.3 µg/day), zinc (4.8 vs. 6.4 mg/day), iron (16.6 vs. 29.6 mg/day), lower plasma selenium (0.72 vs. 1.60 µmol/L), and higher body iron (5.3 vs. 3.8 mg/kg), although plasma zinc was similar (8.60 vs. 8.87 µmol/L). Body iron and plasma zinc were positive determinants of hemoglobin. CONCLUSION: Risk of zinc deficiency was higher than ID and was shown not to be associated with selenium status. Plasma zinc was almost as important as body iron as a hemoglobin determinant.

Evidence for an enhancing effect of alginate on iron availability in Caco-2 cells.

The potential use of alginates as a vehicle for water-soluble (bioavailable) iron for fortifying food products was examined using a Caco-2 cell model system. Cell monolayers were exposed to alginates with various mannuronic to guluronic acid ratios at three different concentrations, and cellular ferritin was measured as a surrogate marker of iron uptake into the cell. Ferritin concentrations were significantly higher when the cells were treated with ferric ammonium citrate and 0.5 and 1% w/v (but not 0.1%) alginate, but were unaffected by mannuronic/guluronic acid ratios. The enhancing effect of ascorbic acid was maintained with 0.1% alginate and significantly increased with 0.5 and 1% alginate, whereas the inhibitory effect of tannic acid was significantly reduced with 0.5% alginate. Alginate beads delivered available iron to Caco-2 cells, indicating that they are a promising vehicle for soluble iron with potential use in food fortification programs.