scholarly journals Transfusional iron overload and intravenous iron infusions modify the mouse gut microbiota similarly to dietary iron

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Francesca La Carpia ◽  
Boguslaw S. Wojczyk ◽  
Medini K. Annavajhala ◽  
Abdelhadi Rebbaa ◽  
Rachel Culp-Hill ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Iron Overload ◽  
Iron Status ◽  
Intravenous Iron ◽  
Dietary Iron ◽  
Microbial Metabolites ◽  
Biologically Relevant ◽  
Iron Stores ◽  
Iron Administration ◽  
Mouse Gut Microbiota

Abstract Iron is essential for both microorganisms and their hosts. Although effects of dietary iron on gut microbiota have been described, the effect of systemic iron administration has yet to be explored. Here, we show that dietary iron, intravenous iron administration, and chronic transfusion in mice increase the availability of iron in the gut. These iron interventions have consistent and reproducible effects on the murine gut microbiota; specifically, relative abundance of the Parabacteroides and Lactobacillus genera negatively correlate with increased iron stores, whereas members of the Clostridia class positively correlate with iron stores regardless of the route of iron administration. Iron levels also affected microbial metabolites, in general, and indoles, in particular, circulating in host plasma and in stool pellets. Taken together, these results suggest that by shifting the balance of the microbiota, clinical interventions that affect iron status have the potential to alter biologically relevant microbial metabolites in the host.

The influence of high-altitude living on body iron

Blood ◽  
2005 ◽  
Vol 106 (4) ◽  
pp. 1441-1446 ◽  
Author(s):  
James D. Cook ◽  
Erick Boy ◽  
Carol Flowers ◽  
Maria del Carmen Daroca
Keyword(s):  
Standard Error ◽  
Transferrin Receptor ◽  
Quantitative Assessment ◽  
Iron Status ◽  
Dietary Iron ◽  
Body Iron ◽  
Iron Stores ◽  
Iron Deficient ◽  
Iron Based ◽  
Maternal Iron

Abstract The quantitative assessment of body iron based on measurements of the serum ferritin and transferrin receptor was used to examine iron status in 800 Bolivian mothers and one of their children younger than 5 years. The survey included populations living at altitudes between 156 to 3750 m. Body iron stores in the mothers averaged 3.88 ± 4.31 mg/kg (mean ± 1 SD) and 1.72 ± 4.53 mg/kg in children. No consistent effect of altitude on body iron was detected in children but body iron stores of 2.77 ± 0.70 mg/kg (mean ± 2 standard error [SE]) in women living above 3000 m was reduced by one-third compared with women living at lower altitudes (P < .001). One half of the children younger than 2 years were iron deficient, but iron stores then increased linearly to approach values in their mothers by 4 years of age. When body iron in mothers was compared with that of their children, a striking correlation was observed over the entire spectrum of maternal iron status (r = 0.61, P < .001). This finding could provide the strongest evidence to date of the importance of dietary iron as a determinant of iron status in vulnerable segments of a population. (Blood. 2005;106:1441-1446)

Inherited and Acquired Modifiers of Iron Status May Dramatically Affect the Phenotypic Expression of Dehydrated Hereditary Stomatocytosis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1281-1281
Author(s):  
Corentin Orvain ◽  
Lydie Da Costa ◽  
Richard van Wijk ◽  
Serge Pissard ◽  
Veronique Picard ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Iron Overload ◽  
Hemolytic Anemia ◽  
Iron Status ◽  
Phenotypic Expression ◽  
Wild Type ◽  
Clinical Prognosis ◽  
Normal Value ◽  
Iron Stores ◽  
The Impact

Abstract Background: Hereditary stomatocytosis is an inherited disorder of the erythrocyte membrane responsible of chronic hemolytic anemia. Recent advances in the understanding of this group of diseases came from the identification of the molecular basis of this disorder. Mutations in the SLC4A1, FAM38A, RHAG, and SLC2A1 genes have been shown to cause different subtypes of hereditary stomatocytosis. Dehydrated hereditary stomatocytosis (DHSt) is due to mutations in the FAM38A gene coding for the mechanotransduction protein PIEZO1 and to the newly discovered mutations in the KCNN4 gene encoding the Gardos channel. It is important to recognize this entity and differentiate it from hereditary spherocytosis as patients with HSt develop severe and sometimes lethal thromboembolic complications following splenectomy. Also, some patients develop progressive and severe iron overload (IO) despite well compensated hemolysis and no or little transfusion requirement. It is unclear why patients have such different clinical features regarding hemolytic anemia and IO. We describe herein the impact of inherited and acquired modifiers of iron status on the phenotypic expression of DHSt. Patients & Methods: We describe four patients (3 related and 1 unrelated) with proven DHSt due to FAM38A mutations, who displayed varying degrees of iron load. Results: The four reported patients were referred to our specialized outpatient consultation (center of expertise on rare iron overload) for investigation. Their clinical, laboratory and radiological features are summarized in the Table. It is noteworthy that both index cases were initially referred for investigation of hyperferritinemia. Iron levels closely correlated with the degree of hemolysis and with the severity of the clinical complications. One female patient with severe iron overload suffered from chronic anemia, acute hemolytic episodes, and symptomatic gallstones requiring cholecystectomy while one male patient with severe iron overload suffered from a thrombotic event. The two other female patients with no or moderate iron overload had no or mild hemolysis. Genetic modifiers increasing iron stores, such as the presence of the HFE C282Y mutation, and possibly the gender (male), were accompanied with higher liver iron concentration, increased hemolysis and clinical manifestations. On the opposite, females with normal or low iron stores (iron deficiency anaemia (ID) due to gynecologic bleedings) displayed no or mild hemolytic manifestations. It is noteworthy that in the female with ID no clinical or biological manifestations of hemolysis and of stomatocytosis were found initially (normal specialized phenotypic tests). The diagnosis was made by genetic analyses. Restoration of the iron stores resulted in the appearance of biological signs of hemolysis. Conclusion: Iron overload or iron deficiency dramatically alter the clinical presentation of DHST due to PIEZO1 defects. The search for genetic or acquired causes of iron overload (or deficiency) is an important step in the evaluation of the clinical prognosis and the modulation of iron store may help in the management of the patients. Table Clinical, biological, and radiological characteristics of the 4 patients N: normal value; NA: not available; wt: wild-type; ID: iron deficiency Table. Clinical, biological, and radiological characteristics of the 4 patients. / N: normal value; NA: not available; wt: wild-type; ID: iron deficiency Disclosures Cartron: Roche: Consultancy, Honoraria; Celgene: Honoraria; Gilead: Honoraria; Jansen: Honoraria.

The assessment of serum nontransferrin-bound iron in chelation therapy and iron supplementation

Blood ◽  
2000 ◽  
Vol 95 (9) ◽  
pp. 2975-2982 ◽  
Author(s):  
William Breuer ◽  
Aharon Ronson ◽  
Itzchak N. Slotki ◽  
Ayala Abramov ◽  
Chaim Hershko ◽  
...  
Keyword(s):  
Iron Overload ◽  
Iron Status ◽  
Hereditary Hemochromatosis ◽  
Intravenous Iron ◽  
Iron Chelator ◽  
Enzyme Linked Immunosorbent Assay ◽  
Simple Method ◽  
Stage Renal Disease ◽  
End Stage ◽  
Iron Chelator Deferoxamine

Nontransferrin-bound iron (NTBI) appears in the serum of individuals with iron overload and in a variety of other pathologic conditions. Because NTBI constitutes a labile form of iron, it might underlie some of the biologic damage associated with iron overload. We have developed a simple method for NTBI determination, which operates in a 96-well enzyme-linked immunosorbent assay format with sensitivity comparable to that of previous assays. A weak ligand, oxalic acid, mobilizes the NTBI and mediates its transfer to the iron chelator deferoxamine (DFO) immobilized on the plate. The amount of DFO-bound iron, originating from NTBI, is quantitatively revealed in a fluorescence plate reader by the fluorescent metallosensor calcein. No NTBI is found in normal sera because transferrin-bound iron is not detected in the assay. Thalassemic sera contained NTBI in 80% of the cases (range, 0.9-12.8 μmol/L). In patients given intravenous infusions of DFO, NTBI initially became undetectable due to the presence of DFO in the sera, but reappeared in 55% of the cases within an hour of cessation of the DFO infusion. This apparent rebound was attributable to the loss of DFO from the circulation and the possibility that a major portion of NTBI was not mobilized by DFO. NTBI was also found in patients with end-stage renal disease who were treated for anemia with intravenous iron supplements and in patients with hereditary hemochromatosis, at respective frequencies of 22% and 69%. The availability of a simple assay for monitoring NTBI could provide a useful index of iron status during chelation and supplementation treatments.

Iron status in Danish women, 1984-1994: a cohort comparison of changes in iron stores and the prevalence of iron deficiency and iron overload

2003 ◽  
Vol 71 (1) ◽  
pp. 51-61 ◽  
Author(s):  
Nils Milman ◽  
Keld-Erik Byg ◽  
Lars Ovesen ◽  
Marianne Kirchhoff ◽  
Kirsten S-L Jürgensen
Keyword(s):  
Iron Deficiency ◽  
Iron Overload ◽  
Iron Status ◽  
Iron Stores ◽  
Cohort Comparison

The TMPRSS6 Ala736 Val Polymorphism Is Associated With Decreased Hemoglobin and Iron Status In Females Undergoing Repeated Phlebotomy

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 787-787 ◽  
Author(s):  
Alan E. Mast ◽  
John C Langer ◽  
Walter Bialkowski ◽  
Simone Glynn ◽  
Tzong-Hae Lee ◽  
...  
Keyword(s):  
Blood Donors ◽  
Iron Absorption ◽  
Blood Donation ◽  
Iron Status ◽  
Dietary Iron ◽  
Body Iron ◽  
Iron Stores ◽  
First Time ◽  
Average Body ◽  
Average Hemoglobin

Abstract Background Iron depletion and deferral for low hemoglobin occur rapidly in some donors while others can repeatedly donate without deferral. This variation may be partly explained by significant genetic differences that affect regulation of dietary iron absorption and/or hemoglobin level following blood donation. Previous studies have found that the C282Y and H63D hemochromatosis mutations do not improve dietary iron absorption following donation. TMPRSS6 is a membrane-associated serine protease that degrades hemojuvelin, thereby decreasing hepcidin production with consequent increase in dietary iron absorption. Its physiological importance is best demonstrated by the development of iron resistant iron deficiency anemia in those with TMPRSS6 mutations. A common TMPRSS6 polymorphism, A736V (rs855791), is associated with lower hemoglobin, MCV and transferrin saturation. Its correlation with iron status and hemoglobin production was examined in blood donors undergoing repeated phlebotomy. Methods Three sample sets from blood donors with well-characterized demographics, blood donation history, hemoglobin and iron parameters enrolled in the approximately 2-year longitudinal Retrovirus Epidemiology Donor Study-II (REDS-II) Iron Status Evaluation Study (RISE) were selected from the NHLBI BioLINCC repository: (Set 1) a random sample of 200 male and 200 female first-time donors and donors reactivated at study enrollment (no donations for 2 years); (Set 2) 114 first-time females who became “frequent” donors by donating at least 4 times in a 2-year period; and (Set 3) 33 repeat male donors, who were deferred for low hemoglobin during the study. Genetic testing for the TMPRSS6 A736V polymorphism was performed on donors in all 3 sets. Variation of hemoglobin and iron status among genotypes, adjusted for donor age, weight, race/ethnicity, number of donations in the previous 12 months and length of time between donations, was assessed using linear models. Results Genotypic frequencies in Set 1 were 40% AA, 42% A/V and 18% VV. The prevalence was not statistically different in the other two sets of donors, although there was a trend for higher prevalence of VV (30%) in Set 3. Hemoglobin, log-transformed ferritin and body iron stores (calculated based on ferritin and soluble transferring receptor) varied among TMPRSS6 genotypes in females but not in males. For females, average hemoglobin was 0.75 and 0.53 g/dL higher in AA (p<0.0001) and A/V (p=0.0057) than in VV. Average ferritin was 75% and 53% higher in AA (p=0.0024) and A/V (p=0.022) than in VV. Average body iron stores were 2.2 mg/kg and 1.8 mg/kg higher in AA (p=0.0045) and AV (p=0.022) than in VV. For males, average hemoglobin was only 0.13 g/dL higher in AA (p=0.47) and 0.035 g/dL lower in A/V (p=0.83) than in VV. Average ferritin was only 15% higher in AA (p=0.46) and was 8% lower in A/V (p=0.83) than in VV. Average body iron stores were 0.84 mg/kg higher in AA (p=0.10) and 0.15 mg/kg lower in A/V (p=0.75) than in VV. Due to the differences found in females, the longitudinal models were repeated using Set 2 subjects, which confirmed a significant association of the TMPRSS6 polymorphism with hemoglobin in females; 0.50 and 0.35 g/dL higher in AA (p<0.0037) and A/V (p=0.0255) than in VV. However, trends for effects on ferritin and body iron stores did not reach significance. Plasma hepcidin values were also available for Set 2 subjects, but significant differences among TMPRSS6 genotypes were not found. Conclusions The A736V TMPRSS6 polymorphism is associated with significant differences in hemoglobin and iron status of first-time female blood donors after undergoing iron loss from repeated phlebotomy. The apparent difference between males and females in variation among genotypes may be the result of greater baseline iron depletion in females rather than a gender difference per se. This is the first demonstration of an association between a common polymorphism of iron metabolism and altered individual responses to blood donation. The findings are consistent with a model in which the TMPRSS6 genotypes differ in proteolytic activity towards hemojuvelin, thereby altering hepcidin production and dietary iron absorption in otherwise healthy, but iron depleted individuals. Disclosures: Mast: Novo Nordisk: Honoraria, Research Funding.

scholarly journals Plasma Hepcidin Increases with Prolonged Running in Male, but Not Female, Collegiate Distance Runners with Low Iron Stores

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1777-1777
Author(s):  
David Barney ◽  
James Ippolito ◽  
Claire Berryman ◽  
Stephen Hennigar
Keyword(s):  
Serum Ferritin ◽  
Iron Status ◽  
Total Iron ◽  
Negative Regulator ◽  
Dietary Iron ◽  
Iron Intake ◽  
Distance Runners ◽  
Vo2 Max ◽  
Iron Stores ◽  
Males And Females

Abstract Objectives Hepcidin is a negative regulator of extracellular iron availability and dietary iron absorption. Previous studies have shown that hepcidin increases with prolonged endurance exercise, but not in those with low iron stores (serum ferritin &lt;30 ng/mL). The objective of this study was to determine the plasma hepcidin response to exercise, compared to rest, in highly trained male and female collegiate distance runners. Methods In a cross-over design, healthy male (n = 14; age 20.2 ± 1.4 y; BMI 20.4 ± 1.6 kg/m2; VO2 max 69.8 ± 5.6 mL/kg/min) and female (n = 14; age 20.1 ± 1.4 y, P = 0.79; BMI 18.1 ± 1.6 kg/m2, P &lt; 0.001; VO2 max 62.5 ± 4.2 mL/kg/min, P &lt; 0.001) collegiate distance runners performed a bout of running (males: 109.8 ± 8.7 min, 15.0 ± 1.3 miles; females: 87.7 ± 10.4 min, P &lt; 0.0001, 11.3 ± 1.5 miles, P &lt; 0.0001) or no activity (rest) separated by 2 weeks. Indicators of iron status and plasma hepcidin were determined at baseline and three hours after exercise or rest. Dietary iron and total iron intake (dietary iron + iron from supplements) were determined by Food Frequency Questionnaires. Results Serum ferritin (males: 24.0 ± 15.9 ng/mL, females: 19.4 ± 9.5 ng/mL, P = 0.39) and plasma hepcidin (males: 22.3 ± 20.6 ng/mL, females: 24.6 ± 19.6 ng/mL, P = 0.77) did not differ between males and females at baseline. Baseline hemoglobin (males: 14.5 ± 0.8 g/dL, females: 13.4 ± 1.0 g/dL, P &lt; 0.01) and hematocrit (males: 45.3 ± 2.2%, females: 42.1 ± 2.6%, P &lt; 0.01) were greater in males compared to females. Dietary iron intake (males: 18.6 ± 6.3 mg/d, females: 17.1 ± 6.4 mg/d, P = 0.55) and total iron intake (males: 48.7 ± 32.9 mg/d, females: 64.6 ± 32.3 mg/d, P = 0.22) did not differ between males and females. Plasma hepcidin increased with exercise compared to rest in males (change from rest: 30.3 ± 42.0 ng/mL, P = 0.02) but not in females (change from rest: 0.8 ± 32.0 ng/mL, P = 0.93). Change in plasma hepcidin with exercise was correlated with sex (R = 0.380, P = 0.05) and BMI (R = 0.383, P = 0.04), but not baseline ferritin, run time, run distance, hemoglobin, hematocrit, dietary iron, or total iron intake (P &gt; 0.05 for all). Conclusions The post-exercise hepcidin response occurs in male, but not female, collegiate distance runners with low iron stores. These findings indicate that declines in iron status in female distance runners are independent of exercise-induced hepcidin. Funding Sources Intramural funds to S.R.H.

scholarly journals Low Phytate Peas (Pisum sativum L.) Improve Iron Status, Gut Microbiome, and Brush Border Membrane Functionality In Vivo (Gallus gallus)

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2563 ◽  
Author(s):  
Tom Warkentin ◽  
Nikolai Kolba ◽  
Elad Tako
Keyword(s):  
Iron Deficiency ◽  
Gut Microbiota ◽  
Brush Border ◽  
Brush Border Membrane ◽  
Iron Status ◽  
Gallus Gallus ◽  
Intestinal Microbiome ◽  
Physiological Status ◽  
Dietary Iron

The inclusion of pulses in traditional wheat-based food products is increasing as the food industry and consumers are recognizing the nutritional benefits due to the high protein, antioxidant activity, and good source of dietary fiber of pulses. Iron deficiency is a significant global health challenge, affecting approximately 30% of the world’s population. Dietary iron deficiency is the foremost cause of anemia, a condition that harms cognitive development and increases maternal and infant mortality. This study intended to demonstrate the potential efficacy of low-phytate biofortified pea varieties on dietary iron (Fe) bioavailability, as well as on intestinal microbiome, energetic status, and brush border membrane (BBM) functionality in vivo (Gallus gallus). We hypothesized that the low-phytate biofortified peas would significantly improve Fe bioavailability, BBM functionality, and the prevalence of beneficial bacterial populations. A six-week efficacy feeding (n = 12) was conducted to compare four low-phytate biofortified pea diets with control pea diet (CDC Bronco), as well as a no-pea diet. During the feeding trial, hemoglobin (Hb), body-Hb Fe, feed intake, and body weight were monitored. Upon the completion of the study, hepatic Fe and ferritin, pectoral glycogen, duodenal gene expression, and cecum bacterial population analyses were conducted. The results indicated that certain low-phytate pea varieties provided greater Fe bioavailability and moderately improved Fe status, while they also had significant effects on gut microbiota and duodenal brush border membrane functionality. Our findings provide further evidence that the low-phytate pea varieties appear to improve Fe physiological status and gut microbiota in vivo, and they highlight the likelihood that this strategy can further improve the efficacy and safety of the crop biofortification and mineral bioavailability approach.

scholarly journals Traditional Beer Consumption and the Iron Status of Spouse Pairs From a Rural Community in Zimbabwe

Blood ◽  
1997 ◽  
Vol 89 (6) ◽  
pp. 2159-2166 ◽  
Author(s):  
Victor M. Moyo ◽  
Innocent T. Gangaidzo ◽  
Z.A.R. Gomo ◽  
Hlosukwazi Khumalo ◽  
Thokozile Saungweme ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Iron Status ◽  
Transferrin Saturation ◽  
Elevated Serum ◽  
Repeated Measurements ◽  
Dietary Iron ◽  
Beer Consumption ◽  
Vitamin C Supplementation ◽  
The Relationship

Abstract To examine the relationship between dietary iron exposure through the consumption of traditional beer and the presence of iron overload in black Africans not related by birth, we studied 28 husband and wife pairs from a rural Zimbabwean community. Lifetime traditional beer consumption was estimated by questioning subjects and iron status was assessed by repeated measurements of serum ferritin and transferrin saturation in subjects who were fasting and had received vitamin C supplementation. Each of the 56 study subjects had an estimated lifetime traditional beer consumption <1,000 L. The mean ± standard deviation (SD) concentration of iron in the supernatants of nine samples of traditional beer from the community was 46 ± 10 mg/L. Four of 28 men (14.3%) and no women had the combination of an elevated serum ferritin and a transferrin saturation <70%, suggestive of substantial iron overload. Significant correlations were not found between the iron status of the husbands and their wives or between dietary iron exposure and iron stores. Our findings suggest that dietary iron exposure may not fully explain the development of iron overload in Africans and are consistent with the hypothesis that an iron-loading gene may also be implicated in pathogenesis.

Iron status in Danish men 1984-94: a cohort comparison of changes in iron stores and the prevalence of iron deficiency and iron overload

2002 ◽  
Vol 68 (6) ◽  
pp. 332-340 ◽  
Author(s):  
Nils Milman ◽  
Keld-Erik Byg ◽  
Lars Ovesen ◽  
Marianne Kirchhoff ◽  
Kirsten Schultz-Larsen Jurgensen
Keyword(s):  
Iron Deficiency ◽  
Iron Overload ◽  
Iron Status ◽  
Iron Stores ◽  
Cohort Comparison

scholarly journals Dietary intakes of 6–24-month-old urban South Island New Zealand children in relation to biochemical iron status

2002 ◽  
Vol 5 (2) ◽  
pp. 339-346 ◽  
Author(s):  
Patsy Soh ◽  
Elaine L Ferguson ◽  
Joanne E McKenzie ◽  
Sheila Skeaff ◽  
Winsome Parnell ◽  
...  
Keyword(s):  
New Zealand ◽  
Breast Feeding ◽  
Serum Ferritin ◽  
Iron Status ◽  
Dietary Factors ◽  
Food Sources ◽  
Dietary Iron ◽  
Dietary Intakes ◽  
Cross Sectional Survey ◽  
Iron Stores

AbstractObjective:To investigate food sources and intakes of iron, and dietary factors associated with serum ferritin levels in 6–24-month-old children.Design:A cross-sectional survey employing proportionate cluster sampling was conducted in 1998/1999. Dietary intakes were assessed using a non-consecutive 3-day weighed food record. Serum ferritin and C-reactive protein were analysed from non-fasting venepuncture blood samples and general sociodemographic data were collected.Setting:Cities of Christchurch, Dunedin and Invercargill, New Zealand.Subjects:Randomly selected healthy 6–24-month-old non-breast-feeding children (n=226).Results:Total iron intakes (±standard deviation (SD)) among non-breast-feeding infants (<12 months old; n=42) and toddlers (≥12 months old; n=184) were 8.4±2.9 mg day−1 and 5.0±2.5 mg day−1, respectively. Fifteen per cent of infants and 66% of toddlers were at risk of inadequate iron intakes. Main sources of dietary iron were infant formula (60%) for infants and cereals (31%) for toddlers. Meat contributed on average 2% and 10% of dietary iron in the infant and toddler diets, respectively. Dietary factors positively associated with serum ferritin were intakes of iron and vitamin C, whereas intakes of calcium and dietary fibre were negatively associated. For each 1% increase in percentage of energy from iron-fortified formula concomitant with a 1% decrease from dairy products, there was a 4.2% increased odds of replete iron stores (ferritin ≥20 μg l−1).Conclusions:Toddlers were at higher risk of sub-optimal iron intakes than infants. Results suggest that a diet high in bioavailable iron is important for optimising the iron stores of young children in New Zealand.

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