Gut microbiome restoring biogenic ferritin mineral as an effective oral iron supplement for iron deficiency anemia

Traditional iron supplements for iron deficiency anemia (IDA) have several limitations, including suboptimal absorption, gastrointestinal discomfort, and concerns regarding long-term safety. In this study, we synthesized monodisperse 6-line ferrihydrite as an innovative iron supplement, featuring a structure analogous to the natural "iron core" present in ferritin. Notably, 6-line ferrihydrite (6-Fh) was internalized by Caco-2 cells via a process independent of divalent metal transporter 1 (DMT1). Additionally, its stability as nanoparticles within the gastrointestinal tract prevents the irritation typically associated with metal ions, thereby significantly enhancing iron utilization efficiency. Consequently, compared to FeSO₄ (a traditional oral iron supplement), 6-Fh effectively stabilized cellular free iron with low ROS toxicity and high biosafety, thereby effectively maintaining intestinal barrier integrity and avoiding liver injury. Furthermore, it restored intestinal dysbiosis caused by IDA and increased the proportion of beneficial bacterial strains, which was superior to FeSO₄. Characterized by low toxicity, efficient cellular absorption, intestinal stability, and superior iron supplementation efficacy compared with conventional iron supplements, 6-Fh demonstrates compelling therapeutic advantages and holds great promise for medical applications.