Helicobacter hepaticus CdtB promoted brain impairment in BALB/c mice via gut-brain axis

Background Helicobacter hepaticus is highly prevalent in patients with Alzheimer's disease and Parkinson's disease, but the underlying molecular mechanism is still unclear. In this study, we established an animal model of neurodegeneration via infecting BALB/c mice with wild-type H. hepaticus (WT) and CdtB-mutant (ΔCdtB) strains to investigate the influence of CdtB on the progression of cerebral injury. Methods BALB/c mice were infected with either WT or ΔCdtB, and then were euthanized at 6- and 12- months post of infection (MPI). By means of histopathology and molecular biology techniques, we evaluated the colonization of H. hepaticus , colonic and cerebral pathologies, extracellular fibrillary β-amyloid (Aβ) aggregates, antigen responses, blood-brain-barrier (BBB) integrity, selected cytokines and proteins, as well as DNA damage. Results The findings proved that H. hepaticus successfully colonized the intestines, whereas no bacterial DNA was examined in the brains of BALB/c mice. Nevertheless, CdtB antigen was identified in the brains of mice at sampling timepoint. During infection, CdtB exacerbated colonic and cerebral pathologies, compromised BBB integrity to amplify inflammatory responses in the brain, and modified the expression of critical neuronal proteins. Moreover, CdtB was found to induce DNA double-strand breaks (DSBs) and augment Aβ deposition in murine brains at 12 MPI. Conclusions These data indicated that H. hepaticus infection in BALB/c mice may serve as a novel model for investigating neurodegenerative diseases. Furthermore, H. hepaticus CdtB has the potential to exacerbate both neurodegenerative conditions and inflammatory responses.