Restricting iron diet in patients with sickle cell disease prevents organ damage: Study

Many therapies under development aim to reduce systemic iron concentrations in order to alleviate illness consequences, among these iron-induced changes in microbial load and gut integrity are connected and potential therapeutic targets, says an article published in Blood Journal.

Sickle cell disease is a set of hemoglobinopathies characterized by the inheritance of at least one sickle (S) beta-globin gene with another kind of defective hemoglobin. The most frequent of these disorders are sickle cell anemia (HbSS), hemoglobin SC disease (HbSC), and minor and major hemoglobin S thalassemia (HbSthal).

Sickle cell disease (SCD) is a hereditary ailment caused by a -globin gene mutation that causes erythrocyte sickling, vaso-occlusive episodes (VOE), and progressive organ destruction. Chronic hemolysis, inflammation, and red blood cell transfusions can all impair iron homeostasis in SCD. Iron excess occurs in individuals who get many blood transfusions, whereas iron deficiency occurs in another subset of SCD patients.

Huihui Li and colleagues undertook this work in order to explore links between the microbiota, dietary iron, and SCD pathogenesis, we fed SCD mice an iron-restricted diet (IRD).

The key findings of this study were:

1. In SCD mice, IRD therapy reduced iron availability and hemolysis, lowered acute VOE, and improved chronic organ damage.

2. Previous research has shown that the gut bacteria influence illness in SCD mice.

3. IRD modifies microbial load and enhances gut integrity, limiting cross-talk between the gut microbiome and inflammatory factors such old neutrophils and lowering VOE and organ damage.

4. These data support the therapeutic potential of modulating iron homeostasis and the gut flora to improve SCD pathogenesis.

In conclusion, iron overload is a major cause of illness and premature mortality in SCD patients. Dietary iron restriction can be used in conjunction with iron chelating treatment in individuals who require frequent transfusions. This technique is less obvious for the subset of individuals with iron insufficiency and requires confirmation.

Reference:

Li, H., Kazmi, J. S., Lee, S. K., Zhang, D., Gao, X., Maryanovich, M., Torres, L. S., Verma, D., Kelly, L., Ginzburg, Y. Z., Frenette, P. S., & Manwani, D. (2022). Dietary iron restriction protects against vaso-occlusion and organ damage in sickle cell disease. In Blood. American Society of Hematology. https://doi.org/10.1182/blood.2022016218