Dietary Iron Intake Alters Gut Microbiota and Bile Acid Metabolism via FXR Pathway and Gut-Liver Axis

Iron, a vital micronutrient, is central to numerous physiological processes, yet its dietary imbalance has profound implications for gut-liver health and bile acid metabolism, which remain poorly characterized. This study utilized data from the NHANES, KNHANES, and MIMIC-IV databases, revealing a significant association between high dietary iron intake and increased prevalence of diarrhea, fatty liver, and liver fibrosis. In animal models, iron levels in different organs were measured to assess inter-organ dynamics and their implications for health. Key findings indicate that excessive dietary iron disrupts intestinal barrier function, alters gut microbiota composition, reduces bile acid levels, suppresses FXR signaling, and induces liver inflammation. Iron deficiency, though less severe, also causes notable adverse effects. Interventions with chenodeoxycholic acid (CDCA), cholic acid (CA), and fecal microbiota transplantation (FMT) effectively mitigated gut-liver damage and restored FXR signaling pathways. These findings highlight the critical role of dietary iron in gut-liver health, filling key gaps in understanding the dietary iron-microbiota-bile acid axis. It systematically reveals, for the first time, the inter-organ distribution of iron and its impact on gut-liver health, and provides novel therapeutic insights for managing iron-related metabolic disorders.