Western diet linked to brain inflammation and reduced neuroplasticity and memory impairment.

Dysregulated bile acid synthesis and dysbiosis are implicated in Western diet–induced systemic inflammation, microglial activation, and reduced neuroplasticity

long-term WD intake reduced hippocampal synaptic plasticity and the level of brain-derived neurotrophic factor mRNA in the brain and isolated microglia. A WD also activated ERK1/2 and reduced postsynaptic density-95 in the brain, suggesting postsynaptic damage. Moreover, WD-fed mice had increased inflammatory signaling in the brain, ileum, liver, adipose tissue, and spleen, which was accompanied by microglia activation. In the brain, as well as in the digestive tract, a WD reduced signaling regulated by retinoic acid and bile acids (BAs), whose receptors form heterodimers to control metabolism and inflammation. Furthermore, a WD intake caused dysbiosis and dysregulated BA synthesis with reduced endogenous ligands for BA receptors, i.e., farnesoid X receptor and G-protein–coupled bile acid receptor in the liver and brain. Together, dysregulated BA synthesis and dysbiosis were accompanied by systemic inflammation, microglial activation, and reduced neuroplasticity induced by WD