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Parkinson’s disease (PD) is a prevalent neurodegenerative disorder with indistinct etiology and ill-defined pathophysiology. A growing body of reports currently suggests that gut inflammation contributes to the pathogenesis of PD, but the mechanism remains largely unknown. The causes of gut inflammation are miscellaneous. One of such elements is a peripheral infection that can alter gut microbiota composition. <em>Citrobacter rodentium</em> (C.R), a kind of gram-negative bacteria, is an appropriate model organism to study inflammatory bowel disease (IBD) consisting of Ulcerative colitis (UC) and Crohn’s disease (CD). Hence, we hypothesize that C.R infection leading to pro-inflammatory circumstances initiate PD-like injuries or exacerbate the PD pathology in a MPTP-established PD mouse model. <strong>Results:</strong> Primarily, C.R delivery in mice induced an IBD-like symptom, including significant weight loss, increased mortality and water content in feces, gut barrier impairment, intestinal hyperpermeability and inflammation, microbial dysbiosis. Interestingly, C.R challenge altered DA (dopamine) metabolism in the brain via up-regulation the expression of MAOA (monoamine oxidase A) and MAOB (monoamine oxidase B). Secondly, compared to mice with the sole C.R infection or MPTP injection, the combination of C.R and MPTP caused the worse behavioral performances, the over-activation of microglia and astrocyte, the up-regulation of pro-inflammatory cytokines, the breakdown of the blood-brain barrier (BBB), and the dopaminergic degeneration in mice. Mechanistically, the C.R challenge increased the levels of TLR4 in the colon and the striatum. Simultaneously, RNAseq analysis showed the DEGs in the striatum mainly enriches in the PI3K-AKT signaling pathway, which implied the potential involvement of TLR4-PI3K-AKT signaling pathway in the disease condition.