Gold Nanoparticles Regulate Gut Microbiota and Immune Responses for Overcoming Iron Supplementation Side Effects in Anemia Therapy

Iron deficiency anemia (IDA) is a common nutritional deficiency disease caused by iron deficiency. Oral iron supplementation, the simplest and most commonly used iron repletion strategy in the clinic, primarily induces gastrointestinal inflammation, which subsequently elicits complications, including nausea, gastrointestinal bleeding, and constipation. Oral iron supplementation, the most simple and widespread method of iron replenishment in the clinic, primarily causes gastrointestinal inflammation, which, in turn, leads to complications such as nausea, gastrointestinal bleeding, and constipation. Furthermore, gastrointestinal inflammation impedes the absorption of iron, thereby exacerbating anemia. Gold nanoparticles with an inherent anti-inflammatory effect make them a promising weapon for alleviating iron-induced gut inflammation. Herein, we studied the effects of 4,6-diamino-2-pyrimidinethiol (DAPT)-functionalized gold nanoparticles (DAu NPs) on the iron supplementation efficiency and gut inflammation in the IDA model. We discussed the mechanisms of gut microbiota and immune responses on gut inflammation using the 16S rRNA (rRNA) gene sequencing and the polarization of RAW 264.7 cells <i>in vitro</i>. DAu NPs with oral iron supplementation could effectively treat IDA. DAu NPs played a significant role in reshaping gut microbiota, promoting short-chain fatty acid production, and regulating immune responses to reduce inflammation caused by excess iron. <i>In vitro</i>, DAu NPs could inhibit iron-dependent bacteria (<i>Escherichia coli</i>) proliferation while promoting probiotic (<i>Lactobacillus</i>) growth. Oral administration of DAu NPs could regulate M2 polarization of gut macrophages, reduce neutrophil and Th17 cell infiltration, and increase Treg cells recruitment. DAu NPs accumulated primarily in the colon and were excreted via feces, demonstrating excellent biosafety. Our study provides a potential method for the treatment of IDA and other metal element deficiencies.