Dietary iron restriction protects against vaso-occlusion and organ damage in murine sickle cell disease

Huihui Li, Jacob S. Kazmi, Sungkyun Lee, Dachuan Zhang, Xin Gao, Maria Maryanovich, Lidiane Torres, Divij Verma, Libusha Kelly, Yelena Z. Ginzburg, Paul S. Frenette, Deepa Manwani

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Sickle cell disease (SCD) is an inherited disorder resulting from a β-globin gene mutation, and SCD patients experience erythrocyte sickling, vaso-occlusive episodes (VOE), and progressive organ damage. Chronic hemolysis, inflammation, and repeated red blood cell transfusions in SCD can disrupt iron homeostasis. Patients who receive multiple blood transfusions develop iron overload, and another subpopulation of SCD patients manifest iron deficiency. To elucidate connections between dietary iron, the microbiome, and SCD pathogenesis, we treated SCD mice with an iron-restricted diet (IRD). IRD treatment reduced iron availability and hemolysis, decreased acute VOE, and ameliorated chronic organ damage in SCD mice. Our results extend previous studies indicating that the gut microbiota regulate disease in SCD mice. IRD alters microbiota load and improves gut integrity, together preventing crosstalk between the gut microbiome and inflammatory factors such as aged neutrophils, dampening VOE, and organ damage. These findings provide strong evidence for the therapeutic potential of manipulating iron homeostasis and the gut microbiome to ameliorate SCD pathophysiology. Many treatments, which are under development, focus on lowering the systemic iron concentration to relieve disease complications, and our data suggest that iron-induced changes in microbiota load and gut integrity are related- and novel-therapeutic targets.

Original languageEnglish (US)
Pages (from-to)194-199
Number of pages6
JournalBlood
Volume141
Issue number2
DOIs
StatePublished - Jan 12 2023
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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