Excess iron intake induced liver injury: The role of gut-liver axis and therapeutic potential

Excessive iron intake is detrimental to human health, especially to the liver, which is the main organ for iron storage. Excessive iron intake can lead to liver injury. The gut-liver axis (GLA) refers to the bidirectional relationship between the gut and its microbiota and the liver, which is a combination of signals generated by dietary, genetic and environmental factors. Excessive iron intake disrupts the GLA at multiple interconnected levels, including the gut microbiota, gut barrier function, and the liver's innate immune system. Excessive iron intake induces gut microbiota dysbiosis, destroys gut barriers, promotes liver exposure to gut microbiota and its derived metabolites, and increases the pro-inflammatory environment of the liver. There is increasing evidence that excess iron intake alters the levels of gut microbiota-derived metabolites such as secondary bile acids (BAs), short-chain fatty acids, indoles, and trimethylamine N-oxide, which play an important role in maintaining homeostasis of the GLA. In addition to iron chelators, antioxidants, and anti-inflammatory agents currently used in iron overload therapy, gut barrier intervention may be a potential target for iron overload therapy. In this paper, we review the relationship between excess iron intake and chronic liver diseases, the regulation of iron homeostasis by the GLA, and focus on the effects of excess iron intake on the GLA. It has been suggested that probiotics, fecal microbiota transfer, farnesoid X receptor agonists, and microRNA may be potential therapeutic targets for iron overload-induced liver injury by protecting gut barrier function.