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Supplementation with Sucrosomial® iron leads to favourable changes in the intestinal microbiome when compared to ferrous sulfate in mice.

ABSTRACT: Iron deficiency is one of the most common nutritional deficiencies worldwide and is often treated with oral iron supplements. However, commonly used supplements, including those based on ferrous iron salts, are associated with gastrointestinal side effects and unfavorable changes in the intestinal microbiome. Sucrosomial® iron is a novel iron formulation that is effective at treating iron deficiency, and with fewer gastrointestinal side effects, yet its effect on the gut microbiome has not been examined previously. Thus, we treated mice for two weeks with diets containing either Sucrosomial® iron or ferrous sulfate as the sole iron source and examined bacterial communities in the intestine using 16S Microbial Profiling of DNA extracted from feces collected both prior to and following dietary treatment. Mice treated with Sucrosomial® iron showed an increase in Shannon diversity over the course of the study. This was associated with a decrease in the abundance of the phylum Proteobacteria, which contains many pathogenic species, and an increase in short chain fatty acid producing bacteria such as Lachnospiraceae, Oscillibacter and Faecalibaculum. None of these changes were observed in mice treated with ferrous sulfate. These results suggest that Sucrosomial® iron may have a beneficial effect on the intestinal microbiome when compared to ferrous sulfate and that this form of iron is a promising alternative to ferrous iron salts for the treatment of iron deficiency.

SUBMITTER: Zakrzewski M

PROVIDER: S-EPMC8803775 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background:Iron deficiency anemia (IDA) is a widespread nutritional deficiency, and iron supplementation, especially with ferrous sulfate (FeSO4), is the most common strategy to treat IDA; however, compliance is often poor with daily FeSO4 owing to negative side effects. In a previous study, iron from iron-enriched Aspergillus oryzae [Ultimine® Koji Iron (ULT)] was absorbed similarly to FeSO4. Objectives:The main objective of this study was to assess the safety of consuming ULT in terms of increasing non-transferrin-bound iron (NTBI) and gastrointestinal distress. Methods:Young female participants (n = 16) with serum ferritin <40 ?g/L were randomly assigned to a double-blind, 9-wk crossover study with a 3-wk placebo/washout period between treatments. Oral FeSO 4 and ULT supplements containing 65 mg Fe were administered daily for 21 consecutive days. On day 1, serum iron (SI), percentage transferrin saturation (%TS), and NTBI were measured for 8 h on the first day of iron consumption. Changes in biochemical indicators were evaluated after 3 wk consumption. Side effects questionnaires were completed weekly on 2 randomly selected weekdays and 1 weekend day for the entire study. Results:SI, %TS, and NTBI were all markedly higher during hours 2-8 (P < 0.001) with FeSO4 than with ULT. Oxidative stress, inflammatory, and kidney and liver function markers remained unchanged with both supplementations compared with placebo. Changes in iron status markers were not significantly different among the 3 treatments. Individual or global side effects were not significantly different among all treatments. Even when common side effects of nausea, constipation, and diarrhea were combined, FeSO4 treatment had a significantly higher effect than ULT (P = 0.04) and placebo (P = 0.004) only at week 3, but the difference was not significant between ULT and placebo. Conclusions:Low NTBI production and fewer common gastrointestinal side effects with ULT suggest that it is a safe oral iron supplement to treat IDA. This trial was registered at clinicaltrials.gov as NCT04018300.

Project description:Iron has been implicated in the pathogenesis of retinal degenerative diseases, including ocular siderosis. However, the mechanisms of iron-induced retinal toxicity are incompletely understood. Previous work shows that intravitreal injection of Fe2+ leads to photoreceptor (PR) oxidative stress, resulting in PR death within 14 days, and cones are more susceptible than rods to iron-induced oxidative damage. In order to further investigate the mechanism of intravitreal iron-induced retinal toxicity and shed light on mechanisms of iron-induced retinopathy in other mouse models, Fe2+, Fe3+, or saline were injected into the vitreous of adult wild-type mice. Pre-treatment with Ferrostatin-1 was used to investigate whether iron-induced retinal toxicity resulted from ferroptosis. Color and autofluorescence in vivo retinal imaging and optical coherence tomography were performed on day 2 and day 7 post-injection. Eyes were collected for quantitative PCR and Western analysis on day 1 and for immunofluorescence on both day 2 and 7. In vivo imaging and immunofluorescence revealed that Fe2+, but not Fe3+, induced PR oxidative damage and autofluorescence on day 2, resulting in PR death and retinal pigment epithelial cell (RPE) autofluorescence on day 7. Quantitative PCR and Western analysis on day 1 indicated that both Fe2+ and Fe3+ induced iron accumulation in the retina. However, only Fe2+ elevated levels of oxidative stress markers and components of ferroptosis in the retina, and killed PRs. Ferrostatin-1 failed to protect the retina from Fe2+-induced oxidative damage. To investigate the mechanism of Fe2+-induced RPE autofluorescence, rd10 mutant mice aged 6 weeks, with almost total loss of PRs, were given intravitreal Fe2+ or Fe3+ injections: neither induced RPE autofluorescence. This result suggests Fe2+-induced RPE autofluorescence in wild-type mice resulted from phagocytosed, oxidized outer segments. Together these data suggest that intraretinal Fe2+ causes PR oxidative stress, leading to PR death and RPE autofluorescence.

Project description:The similarities between swine and humans in physiological and genomic patterns, as well as significant correlation in size and anatomy, make pigs an useful animal model in nutritional studies during pregnancy. In humans and pigs iron needs exponentially increase during the last trimester of pregnancy, mainly due to increased red blood cell mass. Insufficient iron supply during gestation may be responsible for the occurrence of maternal iron deficiency anemia and decreased iron status in neonates. On the other hand, preventive iron supplementation of non-anemic mothers may be of potential risk due to iron toxicity. Several different regimens of iron supplementation have been applied during pregnancy. The majority of oral iron supplementations routinely applied to pregnant sows provide inorganic, non-heme iron compounds, which exhibit low bioavailability and intestinal side effects. The aim of this study was to check, using pig as an animal model, the effect of sucrosomial ferric pyrophosphate (SFP), a new non-heme iron formulation on maternal and neonate iron and hematological status, placental transport and pregnancy outcome; Methods: Fifteen non-anemic pregnant sows were recruited to the experiment at day 80 of pregnancy and randomized into the non-supplemented group (control; n = 5) and two groups receiving oral iron supplementation-sows given sucrosomial ferric pyrophosphate, 60 mg Fe/day (SFP; n = 5) (SiderAL®, Pisa, Italy) and sows given ferrous sulfate 60 mg Fe/day (Gambit, Kutno, Poland) (FeSO4; n = 5) up to delivery (around day 117). Biological samples were collected from maternal and piglet blood, placenta and piglet tissues. In addition, data on pregnancy outcome were recorded.; Results: Results of our study show that both iron supplements do not alter neither systemic iron homeostasis in pregnant sows nor their hematological status at the end of pregnancy. Moreover, we did not detect any changes of iron content in the milk and colostrum of iron supplemented sows in comparison to controls. Neonatal iron status of piglets from iron supplemented sows was not improved compared with the progeny of control females. No statistically significant differences were found in average piglets weight and number of piglets per litter between animals from experimental groups. The placental expression of iron transporters varied depending on the iron supplement.

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Supplementation with Sucrosomial® iron leads to favourable changes in the intestinal microbiome when compared to ferrous sulfate in mice.

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