The Impacts of Iron Overload and Ferroptosis on Intestinal Mucosal Homeostasis and Inflammation

Intestinal homeostasis is maintained through the interplay of the intestinal mucosa, local and systemic immune factors, and the microbial content of the gut. Iron is a trace mineral in most organisms, including humans, which is essential for growth, systemic metabolism and immune response. Paradoxically, excessive iron intake and/or high iron status can be detrimental to iron metabolism in the intestine and lead to iron overload and ferroptosis-programmed cell death mediated by iron-dependent lipid peroxidation within cell membranes, which contributes to several intestinal diseases. In this review, we comprehensively review recent findings on the impacts of iron overload and ferroptosis on intestinal mucosal homeostasis and inflammation and then present the progress of iron overload and ferroptosis-targeting therapy in intestinal diseases. Understanding the involved mechanisms can provide a new understanding of intestinal disease pathogenesis and facilitate advanced preventive and therapeutic strategies for intestinal dysfunction and diseases.