Fusobacterium nucleatum infection-induced neurodegeneration and abnormal gut microbiota composition in Alzheimer's disease-like rats.

Abstract

ObjectiveTo explore whether Fusobacterium nucleatum could lead to behavioral and pathological changes in Alzheimer’s disease (AD)-like model rat and whether they could affect the gut microbiota.MethodsThe cognitive ability and alveolar bone loss of Sprague-Dawley (SD) rats were tested by Morris water maze and Micro-CT, respectively. HE staining and immunohistochemistry were used to analyze the pathological changes and Aβ1–42 in brains. Western blot was applied to detect the expression of p-Tau 181 in the brain. Limulus amebocyte lysate assay and PCR were performed to determine serum LPS level and whether F. nucleatum accessed the brain, respectively. The gut microbiota was analyzed by the 16S rRNA gene sequence.ResultsOral infection with F. nucleatum could induce increased alveolar bone loss and learning impairment in AD-like rats. Additionally, F. nucleatum exposure increased the Aβ1–42 expression by about one-fourth (P < 0.05), p-Tau181 by about one-third (P < 0.05), and serum LPS (P < 0.05) in AD-like rats. Moreover, F. nucleatum could change the gut microflora composition in AD-like rats, accompanied by a significant increase in the abundance of Streptococcus and Prevotella.ConclusionOral infection with F. nucleatum could contribute to abnormalities in cognitive ability and pathological change in the brain of AD-like rats, which may be related to abnormal gut microbiota composition.