The gut microbiota-brain axis in neurological disorder

Abstract

The gut microbiota (GM) plays an important role in the physiology and pathology of the host. Microbiota communicate with different organs of the organism by synthesizing hormones and regulating body activity. The interaction of the central nervous system (CNS) and gut signaling pathways includes chemical, neural immune and endocrine routes. Alteration or dysbiosis in the gut microbiota leads to different gastrointestinal tract disorders that ultimately impact host physiology because of the abnormal microbial metabolites that stimulate and trigger different physiologic reactions in the host body. Intestinal dysbiosis leads to a change in the bidirectional relationship between the CNS and GM, which is linked to the pathogenesis of neurodevelopmental and neurological disorders. Increasing preclinical and clinical studies/evidence indicate that gut microbes are a possible susceptibility factor for the progression of neurological disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS) and autism spectrum disorder (ASD). In this review, we discuss the crucial connection between the gut microbiota and the central nervous system, the signaling pathways of multiple biological systems and the contribution of gut microbiota-related neurological disorders.

Keywords: gut dysbiosis; gut-brain axis; microbiota; neurological disorders; signaling pathways.

Figure 1

The physiological homeostasis attained during typical brain functioning is a result of the interactions between the brain and the gut-brain (gut microbiota). Several brain disorders, including Parkinson’s disease, neurodegenerative diseases, depression, stress, Alzheimer’s disease, and neurodevelopmental disorders, have been linked to altered gut microbiota or gut dysbiosis.

Figure 2

Communication pathways between the brain and gut microbiota. The interaction between the central nervous system (CNS) and gut microorganisms is mediated via several direct and indirect gut-brain axis mechanisms. They include the immune pathway (including cytokines), short-chain fatty acids and microbial metabolites; the neuroactive pathway, including neurotransmitters and neuroactive metabolites; the neural pathway [enteric nervous system, vagus nerve, and spinal nerves (Sgritta et al., 2019); and the endocrine pathway, hypothalamic pituitary adrenal axis (HPA) (Lyte, 2014b)]. HPA axis response that involves neurons of the hypothalamus that release hormones such as corticotropin receptor hormone (CRH) into the portal circulation or the brain, causing the release of the hormone adrenocorticotropic hormone (ACTH), which starts the production of cortisol and its release. The neuroimmune signaling reactions are regulated by cortisol.