The Microbiota-Gut-Brain Axis in Psychiatric Disorders

Abstract

Modulating the gut microbiome and its influence on human health is the subject of intense research. The gut microbiota could be associated not only with gastroenterological diseases but also with psychiatric disorders. The importance of factors such as stress, mode of delivery, the role of probiotics, circadian clock system, diet, and occupational and environmental exposure in the relationship between the gut microbiota and brain function through bidirectional communication, described as "the microbiome-gut-brain axis", is especially underlined. In this review, we discuss the link between the intestinal microbiome and the brain and host response involving different pathways between the intestinal microbiota and the nervous system (e.g., neurotransmitters, endocrine system, immunological mechanisms, or bacterial metabolites). We review the microbiota alterations and their results in the development of psychiatric disorders, including major depressive disorder (MDD), schizophrenia (SCZ), bipolar disorder (BD), autism spectrum disorder (ASD), and attention-deficit hyperactivity disorder (ADHD).

Keywords: attention-deficit hyperactivity disorder; autism spectrum disorder; bipolar disorder; host response; major depressive disorder; microbiota; schizophrenia.

Figure 1

The bidirectional communication of the microbiota–gut–brain axis is mediated by the immune, neuroendocrine, and neuronal pathways. The activation of the hypothalamic–pituitary–adrenal (HPA) axis is associated with the occurrence of stress factors or dysbiosis, which increase the release of corticotropin-releasing hormone (CRH) from the hypothalamus, which subsequently stimulates the transport of adrenocorticotropic hormone (ACTH) from the anterior pituitary. Under the influence of ACTH, the adrenal gland begins to produce and secrete the stress hormone (cortisol), which is responsible for the modulation of intestinal immune and barrier functions. Figure was created using the Vectornator application.

Figure 2

Metabolism of tryptophan through different pathways: the kynurenine pathway that leads to the production of kynurenine and its derivatives in reliance on indoleamine 2,3-dioxygenase (IDO); the serotonin pathway, including the enterochromaffin cells (ECCs) in which tryptophan is transformed into serotonin (5-HT) and its derivatives and is dependent on short-chain fatty acids (SCFAs) which are biosynthesized by spore-forming Clostridiales. ECCs can be activated by the autonomic nervous system (ANS) to secrete 5-HT into the gut lumen, where it can communicate with the intestinal microbiota. Figure was created using the Vectornator application.