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It has been shown that the Western diet (WD) induces systemic inflammation and cognitive decline. Moreover, probiotic supplementation and antibiotic treatment reduce diet-induced hepatic inflammation. The current study examines whether shaping the gut microbes by <i>Bifidobacterium infantis</i> (<i>B. infantis</i>) supplementation and antibiotic treatment reduce diet-induced brain inflammation and improve neuroplasticity. Furthermore, the significance of bile acid (BA) signaling in regulating brain inflammation was studied. Mice were fed a control diet (CD) or WD for seven months. <i>B. infantis</i> was supplemented to WD-fed mice to study brain inflammation, lipid, metabolomes, and neuroplasticity measured by long-term potentiation (LTP). Broad-spectrum coverage antibiotics and cholestyramine treatments were performed to study the impact of WD-associated gut microbes and BA in brain inflammation. Probiotic <i>B. infantis</i> supplementation inhibited diet-induced brain inflammation by reducing IL6, TNFα, and CD11b levels. <i>B. infantis</i> improved LTP and increased brain PSD95 and BDNF levels, which were reduced due to WD intake. Additionally, <i>B. infantis</i> reduced cecal cholesterol, brain ceramide and enhanced saturated fatty acids. Moreover, antibiotic treatment, as well as cholestyramine, diminished WD-induced brain inflammatory signaling. Our findings support the theory that intestinal microbiota remodeling by <i>B. infantis</i> reduces brain inflammation, activates BA receptor signaling, and improves neuroplasticity.