Increasing evidence indicates that chronic inflammation due to periodontal disease is associated with progression of non-alcoholic fatty liver disease (NAFLD) caused by a Western diet. NAFLD has also been associated with oral infection with the etiological agent of periodontal disease, . oral infection has been shown to induce cardiometabolic disease features including hepatic lipid accumulation while also leading to dysbiosis of the gut microbiome. However, the impact of infection on the gut microbiota of mice with diet-induced NAFLD and the potential for those changes to mediate NAFLD progression has yet to be determined. In the current study, we have demonstrated that infection induced sustained alterations of the gut microbiota composition and predicted functions, which was associated with the promotion of NAFLD in steatotic mice. Reduced abundance of short-chain fatty acid-producing microbiota was observed after both acute and chronic infection. Collectively, our findings demonstrate that infection produces a persistent change in the gut microbiota composition and predicted functions that promotes steatosis and metabolic disease.