The Microbiota-Gut-Brain Axis in Depression: The Potential Pathophysiological Mechanisms and Microbiota Combined Antidepression Effect

Abstract

Depression is a kind of worldwide mental illness with the highest morbidity and disability rate, which is often accompanied by gastrointestinal symptoms. Experiments have demonstrated that the disorder of the intestinal microbial system structure plays a crucial role in depression. The gut-brain axis manifests a potential linkage between the digestion system and the central nervous system (CNS). Nowadays, it has become an emerging trend to treat diseases by targeting intestinal microorganisms (e.g., probiotics) and combining the gut-brain axis mechanism. Combined with the research, we found that the incidence of depression is closely linked to the gut microbiota. Moreover, the transformation of the gut microbiota system structure is considered to have both positive and negative regulatory effects on the development of depression. This article reviewed the mechanism of bidirectional interaction in the gut-brain axis and existing symptom-relieving measures and antidepression treatments related to the gut microbiome.

Keywords: depression; gut microbiota; gut–brain axis; probiotics.

Figure 1

The communication pathway of the gut–brain axis in a depression patient. The HPA axis is activated under internal or external pressure [72]. The hypothalamus activates the release of CRH, promotes the release of ACTH by the pituitary gland, and results in the release of cortisol by the adrenal gland [72]. Cortisol is a hormone that affects intestinal integrity, motility, and mucus production, inducing changes in the composition of intestinal microbiota. In patients with depression, this pathway is significantly enhanced and HPA axis activity is overactive [73]. The end result is often IBS and disrupted gut microbiota. Microbial metabolites including short-chain fatty acids and microbial neural substrates such as catecholamines, histamines, and GABA can act on intestinal epithelial cells and stimulate intestinal nerves, which will stimulate the central nervous system through the vagus nerve [74]. Some SCFAs and peptide can cross the blood–brain barrier and act directly on the central nervous system. LPS on the surface of Gram-negative bacteria can mediate the effects of immune cells and the vagus nerve on the brain [75]. HPA, hypothalamus–pituitary–adrenal; CRH, corticotropin-releasing hormone; ACTH, adrenocorticotropic hormone; CNS, central nervous system; GABA, γ-aminobutyric acid; SCFA, short-chain fatty acid; LPS, lipopolysaccharide; IBS, irritable bowel syndrome.