Fig. 1

Overview of the gut microbiome-brain axis. Communications between the gut microbiome and the central nervous system (CNS) involve circulatory, immunological, vagus nerve, lymphatic and glymphatic, and neuro-endocrine (hypothalamic-pituitary-adrenal [HPA] axis) pathways. Gut microbes, their products (pathogen-associated molecular pattern [PAMPs] and extracellular vesicles) and metabolites, and gut neurotransmitters and hormones secreted by enteroendocrine cells, can transport to the CNS via peripheral circulation and impaired blood-brain barrier; they also interact with the host immune system and affect the CNS via blood circulation or lymphatic and glymphatic system. In addition, microbes and bacterial DNA can also translocate into the mesenteric lymphatic nodes. The vagus nerve transmits neural signals from the CNS to the gut, and also transports gut signals (activated by metabolites or neurotransmitters and hormones secreted by enteroendocrine cells) or gut microbiome-derived products like extracellular vesicles to the CNS. The HPA axis is a major neuro-endocrine system responding to stress by the release of cortisol from the adrenal cortex, which subsequently regulates the gut immune system and influences the gut microbiome composition. In turn, the gut microbiome can activate the HPA axis. EC enteroendocrine cell, IL interleukin, LPS lipopolysaccharide, SCFAs short-chain fatty acids, Th T helper cell, TNF-α tumour necrosis factor-α