Depression is a complex, heterogeneous psychiatric disorder with multifactorial aetiology. Substantial evidence indicates that depressive episodes are associated not only with changes in neurotransmission in the central nervous system (CNS), but also may lead to structural changes in the brain through neuroendocrine, inflammatory, and immunological mechanisms. Among the factors deserving special attention connected with developing systematic inflammation are altered intestinal permeability, IgG food intolerance, and changes in gut microbiota.

We present a possible scenario of the development of depression, linking elevated zonulin production, loosening of the tight junction barrier, an increase in permeability of the gut wall, and the passage of macromolecules, normally staying the gut, into the bloodstream, with the immuno-inflammatory cascade and induction of IgG-dependent food sensitivity. Alterations in bidirectional signaling between the gastrointestinal tract and the brain, so called “microbiota–gut–brain axis”, may be normalized by dietary immunomodulating factors, including prebiotics and probiotics. In the case of increased IgG concentrations, the implementation of an elimination–rotation diet may prove to be an effective method of reducing inflammation and, in this way, alleviating depressive symptoms.

Given complexity and variety of mood disorders, it is necessary to develop improved integration models. Preliminary study results raise hope that the new methods mentioned above, i.e. psychobiotics, prebiotics, an elimination-rotation diet, may be an important addition to the psychiatrist's armamentarium as therapeutic agents improving the efficacy of the treatment for affective disorders [1–3].