Iron deficiency anemia: a critical review on iron absorption, supplementation and its influence on gut microbiota.

Iron deficiency anemia (IDA) caused by micronutrient iron deficiency has attracted global attention due to its adverse health effects. The regulation of iron uptake and metabolism is finely controlled by various transporters and hormones in the body. Dietary iron intake and regulation are essential in maintaining human health and iron requirements. The review aims to investigate literature concerning dietary iron intake and systemic regulation. Besides, recent IDA treatment and dietary iron supplementation are discussed. Considering the importance of the gut microbiome, the interaction between bacteria and micronutrient iron in the gut is also a focus of this review. The iron absorption efficiency varies considerably according to iron type and dietary factors. Iron fortification remains the cost-effective strategy, although challenges exist in developing suitable iron fortificants and food vehicles regarding bioavailability and acceptability. Iron deficiency may alter the microbiome structure and promote the growth of pathogenic bacteria in the gut, affecting immune balance and human health.

Effects of hemoglobin extracted from Tegillarca granosa on the gut microbiota in iron deficiency anemia mice.

Iron deficiency anemia (IDA) is a serious threat to the health of humans around the world. Tegillarca granosa (T. granosa) is considered as an excellent source of iron due to its abundant iron-binding protein hemoglobin. This study aimed to investigate the effects of hemoglobin from T. granosa on the gut microbiota and iron bioavailability in IDA mice. Compared to normal mice, IDA mice showed reduced microbiota diversity and altered relative abundance (reduced Muribaculaceae and increased Bacteroides). After 4 weeks of administration, hemoglobin restored the dysbiosis of the intestinal microbiota induced by IDA and decreased the Firmicutes/Bacteroidota ratio and the abundance of Proteobacteria. Analysis of the hemoglobin regeneration efficiency of mice treated with hemoglobin confirmed that hemoglobin exhibited high iron bioavailability, particularly at low-dose administration, suggesting that a small amount of hemoglobin from T. granosa markedly elevated the blood hemoglobin level in mice. These findings suggested that IDA could be alleviated by administration of hemoglobin with excellent iron bioavailability, and its therapeutic mechanism may be partially attributed to the regulation of the intestinal microbiota composition and relative abundance. These results indicated that T. granosa hemoglobin may be a promising iron supplement to treat IDA and promote the utilization of aquatic-derived proteins.

Absorption of iron from Tegillarca granosa using an in vitro simulated digestion and Caco-2/HepG2 co-culture system.

BACKGROUND: Iron-deficiency anemia is one severe micronutrient malnutrition and has captured worldwide attention. This study evaluated the in vitro iron absorption of two iron-binding proteins (hemoglobin and ferritin) from Tegillarca granosa. In addition, the protein structure-iron absorption relationship and the regulatory effect of hepcidin on cellular iron absorption were explored. RESULTS: Our findings revealed that both hemoglobin and ferritin extracted from T. granosa contained abundant iron-binding sites, as evidenced by stronger peaks in amide I and II regions compared with the two proteins from humans. Less ß-sheet (27.67%) structures were found in hemoglobin compared with ferritin (36.40%), probably contributing to its greater digestibility and more release of available iron. This was confirmed by the results of Caco-2/HepG2 cell culture system that showed iron absorption of hemoglobin was 26.10-39.31% higher than that of ferritin with an iron content of 50-150 µmol L-1 . This high iron absorption of hemoglobin (117.86-174.10 ng mg-1 ) could also be due to more hepcidin produced by HepG2 cells, thereby preventing ferroportin-mediated iron efflux from Caco-2 cells. In addition, the possible risk of oxidative stress was evaluated in cells post-iron exposure. In comparison with ferrous sulfate, a common iron supplement, Caco-2 cells treated with the iron-binding proteins had a 9.50-25.73% lower level of intracellular reactive oxygen species, indicating the safety of hemoglobin and ferritin. CONCLUSION: Collectively, the data of this research would be helpful for understanding the key features and potential of developing hemoglobin and ferritin from T. granosa as novel iron supplements. © 2022 Society of Chemical Industry.

Efficacy of Pneumatophorus japonicus meat as an iron fortificant in whole-wheat flour in preventing iron deficiency.

Iron deficiency anemia (IDA) is a global health concern affecting one-third of the world's population, particularly those dominated by plant-based food. Fortifying staple foods with iron has been an effective strategy for preventing IDA. Pneumatophorus japonicus is an essential economic fish in China. Pneumatophorus japonicus dark meat is usually underutilized as a byproduct, though it contains bounteous nutrients, including heme iron (10.50 mg/100 g). This study aimed to investigate the iron bioavailability of P. japonicus dark meat and to evaluate its potential as an iron fortifier for whole-wheat flour, a typical staple food, using an in vitro digestion/Caco-2 cell culture system. Our results suggested the excellent iron bioavailability of P. japonicus dark meat in comparison with beef (a heme dietary iron reference), whole-wheat flour (a non-heme dietary iron reference), and FeSO4 (a conventional iron supplement). The addition of P. japonicus dark meat notably enhanced iron solubility, bioavailability, and protein digestibility of whole-wheat flour. The flour-dark meat mixture yielded 1.96 times the iron bioavailability compared to beef per gram. The iron bioavailability was further improved by adding vitamin C, a commonly used dietary factor, at the Vc/iron mass ratio of 2:100-5:100. Our findings reveal the promise of P. japonicus dark meat as a significant source of bioavailable iron, providing a basis for developing fish byproducts as alternatives for iron supplementation. PRACTICAL APPLICATION: This study investigated the iron bioavailability of Pneumatophorus japonicus meat using in vitro digestion/Caco-2 cell culture system. These results could be used to improve the utilization of Pneumatophorus japonicus byproduct (dark meat) and develop the potential of the byproduct as an iron fortifier for whole-wheat flour.

Effect of hemoglobin extracted from Tegillarca granosa on iron deficiency anemia in mice.

Iron deficiency anemia (IDA) is the most common nutritional deficiency in the world. This study was aimed to evaluate the therapeutic effects of hemoglobin from Tegillarca granosa (T. granosa) on IDA in mice. Mice were randomly divided into five groups: a normal control group, an anemia model group, a positive (FeSO4) control group, a low-dose and high-dose hemoglobin groups. After 4-week iron supplements administration, it was observed that hemoglobin at 2.0 mg iron/kg body weight had better restorative effective on IDA mice than that of FeSO4 with regard to routine blood parameters and serum biochemical indicators. Meanwhile, the IDA-caused alterations of organ coefficients and liver morphology were ameliorated in mice after hemoglobin supplementation in a dose-dependent manner. Further correlation analysis of indicators showed that serum ferritin (iron storage protein) and soluble transferrin receptor (cellular iron uptake membrane glycoprotein) were susceptible to iron deficiency, indicating possibledisorder of iron metabolism caused by IDA. And levels of serum ferritin and soluble transferrin receptor were restored after administration of hemoglobin. These findings confirmed the safety and effectiveness of T. granosa derived hemoglobin in alleviating IDA in mice, suggesting its great potential as an alternative for iron supplementation.

Polyphenols extracted from Enteromorpha clathrata alleviates inflammation in lipopolysaccharide-induced RAW 264.7 cells by inhibiting the MAPKs/NF-κB signaling pathways.

ETHNOPHARMACOLOGY RELEVANCE: Enteromorpha has long been recorded in traditional Chinese medicine, with cholesterol-lowering, anti-cancer, anti-inflammatory and antibacterial effects. Recently, we extracted the polyphenol-enriched fraction from Enteromorpha clathrata (E. clathrata) by ethyl acetate (ECPs), and isolated six individual polyphenols from ECPs via high-speed counter-current chromatography (HSCCC) with high-performance liquid chromatography (HPLC). AIM OF THE STUDY: In this study, we explored the anti-inflammatory activity and underlying mechanism of ECPs in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. MATERIALS AND METHODS: ECPs and the six polyphenols were used for nitric oxide (NO) assay to identify the components with potent inflammation inhibitory effect. Enzyme-linked immunosorbent assay (ELISA), quantitative real-time PCR (qPCR), flow cytometry, and Western blot analysis were applied to further investigate their anti-inflammatory effects and underlying mechanism in LPS-stimulated RAW264.7 cells. RESULTS: ECPs and the three individual polyphenols, including (-)-epicatechin, epigallocatechin-3-O-gallate and (-)-epicatechin-3-O-gallate, showed in vitro immunosuppressive activity by altering the cell biology at the gene, protein and functional levels in a dose- and species-dependent manner. Their anti-inflammatory effects were achieved by inhibiting LPS-induced production of nitric oxide and its upstream enzyme inducible nitric oxide synthase (iNOS), the pro-inflammatory cytokines including interleukin-1 beta (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), as well as the phagocytotic capacity, without cytotoxicity. The mechanism study further revealed that these anti-inflammatory properties were, at least partly, attributed to the suppressed activation of nuclear factor-κB (NF-κB) and p38 mitogen-activated protein kinase (MAPK) signaling pathways. CONCLUSIONS: These findings indicated for the first time the correlation between the anti-inflammatory activity of ECPs and NF-κB and MAPK signaling pathways, suggesting that polyphenol-enriched organic fraction of E. clathrata could be potential candidate as therapeutic agent for treating inflammatory diseases.

Effect of ascorbic acid and citric acid on bioavailability of iron from Tegillarca granosa via an in vitro digestion/Caco-2 cell culture system.

Iron deficiency anaemia (IDA) has been receiving worldwide attention. Developing safe and effective iron supplements is of great significance for IDA treatment. Tegillarca granosa (T. granosa), a traditional aquaculture bivalve species in China, is considered to be an excellent source of micronutrients, but the distribution and bioavailability of these minerals have yet to be investigated. The present research was conducted to determine the contents and in vitro enzymatic digestibility of minerals in T. granosa, using beef and wheat flour as reference foods. Meanwhile, two iron-binding proteins, hemoglobin and ferritin, were extracted from T. granosa, and their structures, iron accessibility and bioavailability were investigated. Moreover, the effects of ascorbic acid (AA) and citric acid (CA), two commonly applied dietary factors, on these parameters were evaluated. Our results indicated that the mineral levels varied significantly among different food matrices, with T. granosa showing the highest contents of the tested elements. Comparison of iron absorption of meat versus wheat flour and hemoglobin versus ferritin confirmed that heme iron exhibited higher bioavailability than non-heme iron. The addition of the two organic acids notably enhanced the cellular iron uptake of T. granosa-derived proteins. This could be because AA/CA weakened hydrogen bonds within proteins and caused disordered secondary structures, thereby improving their enzymatic digestibility and releasing more soluble iron to be available for absorption. The results of this study provided a basis for the development of T. granosa-derived protein-based iron supplements, promoting the diverse utilization of marine aquatic resources.

Structure, functional properties and iron bioavailability of Pneumatophorus japonicus myoglobin and its glycosylation products.

Developing safe and efficient iron supplements is significant for the alleviation of iron-deficient anemia (IDA). Myoglobin (Mb) is a heme-protein rich in bioavailable iron. Pneumatophorus japonicus (P. japonicus), one important economic fish in China, contain a high Mb level in its dark meat normally discarded during processing. The present study aimed to determine the structure, physicochemical properties, and iron bioavailability of Mb extracted from P. japonicus. Meanwhile, the effects of glycosylation, a commonly applied chemical modification of proteins, on these parameters were evaluated. Using Box-Behnken design, the optimal conditions for Mb-chitosan glycosylation were obtained: 45.07 °C, pH 6.10 and Mb/chitosan mass ratio of 6.29. The structure and functional properties of the glycosylated Mb (Mb-gly) were investigated. Compared with the original Mb, Mb-gly obtained a more ordered secondary structure. The surface hydrophobicity of Mb-gly was found to be decreased together with the observations of elevated water solubility. Moreover, glycosylation enhanced the Mb antioxidant capacity, and improved its stability in enzymatic digestion system. Regarding to the iron bioavailability, the cellular uptake of Mb­iron was significantly higher than FeSO4, and further elevated by glycosylation. These results provided a basis for the development of Mb-based iron supplements, promoting the utilization of fish-processing industries wastes.

Functionalized magnetic iron oxide/polyacrylonitrile composite electrospun fibers as effective chromium (VI) adsorbents for water purification.

Inorganic/organic composite electrospun fibers have been extensively investigated as adsorbents for the wastewater treatment. In this study, branched polyethylenimine (b-PEI) functionalized magnetic iron oxide (Fe3O4)/polyacrylonitrile (PAN) composite electrospun fiber adsorbent (b-PEI-FePAN) was fabricated and systematically explored for the removal of toxic hexavalent chromium [Cr(VI)]. b-PEI grafted PAN organic component not only acted as the flexible substrate to load Fe3O4 particles but also made a contribution to the improved adsorption capacity. In the batch adsorption test, the maximum adsorption capacity based on Langmuir fitting was 684.93mg/g, which was higher than most of the reported adsorbents. The removal efficiency could reach above 98% with a dosage of 0.5mg/mL in the real water samples. Moreover, the filtration efficiency was also above 98.5% even at a high flux of 765L·m-2·h-1 in dynamic filtration experiment. According to mechanism analysis, both electrostatic adsorption and reduction action were involved in the Cr(VI) removal processes. These results demonstrate that b-PEI functionalized Fe3O4/PAN composite electrospun fibers have promising potential in water purification field.