The gut–brain axis: The role of melatonin in linking psychiatric, inflammatory and neurodegenerative conditions

Abstract

Recent work has highlighted the importance of immune inflammatory processes, oxidative and nitrosative stress (O&NS) and tryptophan catabolites (TRYCATs) in the aetiology of depression and many depression-associated disorders, including other psychiatric, neurodegenerative and wider medical disorders. A recently researched aspect of the aetiology and course of depression has focussed on the role of gut permeability and gut microbiota. Increased gut permeability is evident in many medical conditions, contributing to increased immune inflammatory cytokines, O&NS and neuroregulatory TRYCATs. By driving tryptophan down the kynurenine pathways and away from serotonin, N-acetylserotonin and melatonin synthesis, such processes alter the nature of central processes, but also contribute to changes in gut permeability regulation. Here we look at the role of decreased melatonin in gut permeability, especially via its regulation of the inflammasome. This has important consequences across a host of medical conditions, including Alzheimer's disease, non-alcoholic fatty liver disease, obesity, fibromyalgia and alcoholism, as well as in the aetiology and course of depression. Such work emphasises the importance of central and systemic interactions, and has implications for the etiological conceptualisation, classification, course and treatment of a diverse array of medical conditions.