Fig. 7

The mechanisms linking the gut-brain axis. Gut microbiota is capable of synthesizing neurotransmitters like SCFAs and GABA, which have different peripheral and central effects on modifying host metabolism and central regulation of appetite directly via vagal stimulation or indirectly through immune-neuroendocrine mechanisms. Enteroendocrine cells are activated by these microbial-derived metabolites, and lead to the production of gut hormones such as 5-hydroxytryptamine (5-HT), GLP-1, PYY, and cholecystokinin (CCK). These gut hormones are released from the gut to the nucleus tractus solitarius of the brain via the vagus nerve and direct secreted into the circulatory system. Information from the nucleus tractus solitarius is distributed to the arcuate nucleus (ARC) in the hypothalamus, where appetite and energy balance are regulated. The ARC contains neuropeptide Y, agouti-related protein, anorexigenic peptides, cocaine amphetamine-regulated transcript, and pro-opiomelanocortin neurons. Moreover, gut microorganisms also use bile acids and their conjugates to activate FXR and TGR5, and increase GLP-1 secretion by enteroendocrine cells. Additionally, gut microbiota is associated with inflammation via the release of LPS, which activates immune cells, such as B cells and dendritic cells, and promotes the production of cytokines. Created with BioRender.com