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Therapeutics for Iron-Related Disorders: Current Approaches and Nutritional Perspectives

A Special Issue of Nutrients (ISSN 2072-6643) belonging to the section "Micronutrients and Human Health".

Deadline for manuscript submissions: 30 December 2026 | Viewed by 1391

Editor

Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA
Interests: mammalian iron metabolism and related disorders; oxygen signaling; colorectal cancer; host–microbiota crosstalk; host micronutrient sensing
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Iron is essential for almost all living organisms. Dietary iron is the only source of iron for mammals, and iron levels must be tightly maintained as imbalance can lead to adverse health outcomes. In humans, iron deficiency and overload disorders are globally prevalent in distinct geographical regions. Iron deficiency is the most common nutritional disorder. About 60% of the total global burden of anemia is represented by iron deficiency anemia (IDA), mainly affecting developing nations. In contrast, iron overload disorders are genetically encoded and are more prevalent (1 in 300 to 500 individuals) in the Western population. Dysregulation of intestinal iron absorption is the hallmark of both deficiency and overload disorders. Currently, our targets for iron-related disorders revolve around the following strategies: (1) Oral or parenteral delivery of iron for anemia. (2) Restriction/removal of iron via chelation or phlebotomy for iron overload. (3) More recently, targeting the hepcidin–Fpn1 axis and hypoxia inducible factor (HIF) pathways for managing both ends of the spectrum. However, strategies for iron-related disorder management are still lacking, and newer approaches specifically targeting aspects of cellular iron flux are warranted. This Special Issue shall focus on the ongoing and upcoming nutritional approaches towards novel therapeutic management of iron-related disorders.

Dr. Nupur Das
Guest Editor

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Keywords

  • intestinal iron absorption
  • intestinal HIF regulation
  • ferritinophagy
  • nutritional aspect of iron homeostasis
  • hereditary disorders of iron absorption
  • gut microbiota

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Published Papers (1 paper)

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Research

13 pages, 1519 KB  
Article
Intestine-Specific Ferroportin Ablation Rescues from Systemic Iron Overload in Mice
by Cristina Castillo, Sharon Gim and Nupur K. Das
Nutrients 2026, 18(2), 352; https://doi.org/10.3390/nu18020352 - 22 Jan 2026
Viewed by 977
Abstract
Background/Objectives: The hepcidin–ferroportin (Fpn1) axis is central to intestinal iron absorption, and dysregulation of this axis underlies all known forms of iron disorders. Hemochromatosis, the most common iron overload disorder in humans, results from systemic iron accumulation due to decades of uncontrolled [...] Read more.
Background/Objectives: The hepcidin–ferroportin (Fpn1) axis is central to intestinal iron absorption, and dysregulation of this axis underlies all known forms of iron disorders. Hemochromatosis, the most common iron overload disorder in humans, results from systemic iron accumulation due to decades of uncontrolled intestinal absorption. Despite major advances in medicine in recent years, strategies for iron overload management are still lagging as they primarily rely on iron chelation and repeated phlebotomies. Fpn1, the cellular iron exporter, is ubiquitously expressed and plays a critical role in maintaining systemic iron homeostasis. Methods: To investigate the specific contribution of intestinal Fpn1 to systemic iron overload, we employed a CRISPR-based adenoviral hepcidin knockout mediated mouse iron overload model, combined with intestine-specific deletion of Fpn1. Results: An initial time-dependent experiment establishes the efficiency of hepcidin knockout (KO) by as early as 1 week of adenovirus injection. At 2 weeks of injection, a perfect reciprocal relationship between hepcidin gene suppression and liver iron levels (5–7-fold induction from the baseline) was established. Finally, intestine-specific Fpn1 deletion effectively prevented iron accumulation in hepcidin KO mice, as evidenced by nearly 4-fold lower liver iron levels compared to hepcidin KO animals with intact intestinal Fpn1. Conclusions: In summary, our results demonstrate that ablation of intestinal Fpn1 is sufficient to attenuate systemic iron accumulation in this mouse model of hemochromatosis. These findings suggest that selective targeting of intestinal Fpn1 may represent a promising strategy for the management of iron overload. Full article
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