Iron deficiency anemia (IDA) is a common nutritional problem, but traditional iron supplements cause many adverse reactions. Thus, the development of a novel iron supplement might be significant for the treatment of IDA. This study aimed to study the transport mechanism of Flammulina velutipes polysaccharide-iron complex (FVP1-Fe(III)) in Caco-2 cells and the therapeutic effect on IDA rats, as well as the influence on gut microbiota in vivo. These results showed that in vitro, the uptake of FVP1-Fe(III) was mediated by sodium-dependent glucose transporter-1 (SGLT1) and facilitated glucose transporter-2 (GLUT2) and GLUT2 played a dominant function. The multidrug resistance-associated protein-2 (MRP-2) was involved in the efflux of FVP1-Fe(III) across the Caco-2 cells. In vivo, FVP1-Fe(III) had a better restorative effect on blood parameters and iron status indicators in rats with IDA as compared with FeSO₄ and exerted this effect by downregulating the expression of hepcidin. FVP1-Fe(III) could also regulate gut microbiota dysbiosis in iron deficiency rats by returning the relative abundance of gut microbiota to the normal level. Besides, as a dietary factor, vitamin C (vit C) could enhance the therapeutic effect of FVP1-Fe(III). These present findings showed that FVP1-Fe(III) could be exploited as a novel iron supplement to treat IDA.

缺铁性贫血 (IDA) 是一种常见的营养问题，但传统的铁补充剂会引起许多不良反应。因此，开发新型铁补充剂可能对 IDA 的治疗具有重要意义。本研究旨在研究金针菇多糖-铁复合物（FVP1-Fe(III)）在Caco-2细胞中的转运机制及对IDA大鼠的治疗作用，以及对体内肠道菌群的影响。这些结果表明，在体外, FVP1-Fe(III) 的摄取由钠依赖性葡萄糖转运蛋白-1 (SGLT1) 介导并促进葡萄糖转运蛋白-2 (GLUT2) 和 GLUT2 发挥主导作用。多药耐药相关蛋白 2 (MRP-2) 参与 FVP1-Fe(III) 通过 Caco-2 细胞的流出。在体内，与 FeSO ₄相比，FVP1-Fe(III) 对 IDA 大鼠的血液参数和铁状态指标具有更好的恢复作用并通过下调 hepcidin 的表达发挥这种作用。FVP1-Fe(III) 还可以通过将肠道微生物群的相对丰度恢复到正常水平来调节缺铁大鼠的肠道微生物群失调。此外，作为饮食因素，维生素C（vit C）可以增强FVP1-Fe（III）的治疗效果。目前的这些发现表明，FVP1-Fe(III) 可用作治疗 IDA 的新型铁补充剂。