Review paper
From gut to depression – the role of intestinal barrier dysfunction and activation of immune system in inflammatory hypothesis of depression

Intestinal permeability dysfunction might be considered either a consequence or cause of systemic inflammation with release of proinflammatory cytokines. A growing body of evidence indicates a key role of the immune system and cytokines in depression. Cytokines cause tryptophan and 5-HT depletion and elevation of neurotoxic tryptophan catabolites by inducing indoleamine 2,3-di-oxygenase (IDO). Another enzyme causing elevation of tryptophan catabolites is tryptophan 2,3-dioxygenase (TDO), which is activated by cortisol, often elevated during depression. Additionally, pro-inflammatory cytokines activate noradrenergic neurotransmission and the HPA axis, and also cause glucocorticoid receptor resistance. There is a growing body of evidence indicating a role of increased intestinal permeability (leaky gut syndrome) in many chronic diseases such as inflammatory bowel diseases, diabetes type I, allergy, asthma, autism, and depression. Numerous investigations indicate that many antidepressant drugs exhibit anti-inflammatory properties by lowering levels of pro-inflammatory cytokines, which might be related to their antidepressant mechanisms of action. A large group of anti-inflammatory substances and antioxidants also exhibit antidepressant potential or potentiate efficacy of antidepressant pharmacotherapy. The aim of the authors of this review is to present a potential relation between increased gut permeability, activation of the inflammatory response system, IgG food allergy (type III hypersensitivity reaction), and depression. Detection of a relationship between IgG-dependent allergy and depression may form the basis for improving the therapeutic scheme.