The gut-brain communicates with the brain mainly via three pathways of the microbiota–gut–brain axis. First, the gut microbiota influences the synthesis and secretion of neurotransmitters, including 5-HT, GABA, DA, NE, Glu, and ACh. Gut signals can activate the ENS and primary afferents as well as transmit messages to the brain through the vagus nerve and the sympathetic nervous system. Second, the gut microbiota impacts the concentration and function of neuropeptides that include neuropeptides, gut peptides, OT, and opioid peptides and neurohormones, such as melatonin, communicating with the brain through the neuroendocrine pathway, including the HPA axis and hypothalamus-pituitary-other peripheral glands axis. Third, the gut microbiota regulates the function of TJs and TLRs in the gut barrier and BBB, adjusts the differentiation of lymphocytes, and impacts the brain via the immune pathway. Additionally, the bioactive products of the microbiota also influence the microbiota–gut–brain axis. The five influential factors on the left protect the microbiota and the mucous layer, leading to the production of beneficial substances, such as SCFA, by the microbiota, which results in an anti-inflammatory environment; meanwhile, the five factors on the right are likely to interrupt the normal function of the gut-brain, which can induce mucus loss and microbiota disturbance, leading to the production of harmful substances such as lipopolysaccharide and NH3 and resulting in a pro-inflammatory environment. NP, Neuropeptides; GP, Gut peptides; OP, Opioid peptides; MT, Melatonin; LPS, lipopolysaccharide; MC, M cell; EC, Enteroendocrine cell.