Attenuating of“Leaky Gut-immune Activation”——A New Pathway in Exercise Alleviating Depressive Neuroinflammation

“Leaky gut”refers to the changes of intestinal permeability caused by stress, high-fat diet, etc., which resulting in the shift of gram-negative bacteria in intestine and generate a series of immune activation. Lipopolysaccharide(LPS) is the main component of intestinal gram-negative bacteria, and it is the main active ingredient of endotoxin as well. Stress can damage the intestinal mucosal barrier and increase gut permeability, so that LPS can be translocated into blood, and then transported by LPSbinding proteins to monocytes and macrophages in serum. After that, LPS will bind to Toll-like receptor 4 receptor-4(TLR4) to activate the body's nervous immune system, and the activation of the immune system in related brain regions may lead to depression. Excessive activation of the TLR4 signaling pathway is one of the triggers of depression. Moderate exercise can weaken the“leaky gut-immune activation-depressive neuroinflammation”, relieve hippocampal neurogenesis and reduce neurotrophic factors. The regulation of“leaky gut-immune activation”by exercise is a potential target for treating depression. The summary of this mechanism will help to correctly understand the role of“gut-brain”dialogue mechanism in the occurrence of depression, and provide more research ideas for exercise intervention in depressive behavior.