Overview of the gut-liver-brain axis with particular emphasis on ferroptosis

Ferroptosis is a form of cellular death involved in the origin, progression, but also regulation of several human diseases. Its regulatory role in the gut-liver-brain axis (GLBA) has not been clarified. Therefore, we sought to summarize the possible correlations between ferroptosis and the GLBA. In this review, we first introduce the phenotype and the main mechanisms of this relatively newly described form of regulated cell death. Then, we analyse the anatomy of the GLBA, describing the connections between the gut and the liver, followed by the anatomical pathways from the gut to the brain and from the liver to the brain. After the morphological aspects, we summarize the main biological modulators of the GLBA, highlighting their physiological and pathological roles. In the end, we discuss in detail the regulatory role of ferroptosis on neuroinflammation and oxidative stress along GLBA, highlighting the key aspects that could be of significant clinical importance as future diagnostic and therapeutic targets.