Prion disease pathogenesis in the absence of the commensal microbiota

Prion diseases are a unique group of transmissible, typically sub-acute, neurodegenerative disorders. During CNS prion disease the microglia become activated and are considered to provide a protective response by scavenging and clearing prions. The mammalian intestine is host to a large burden of commensal microorganisms, especially bacteria, termed the microbiota. The commensal microbiota exerts many beneficial effects on host health including the metabolism of essential nutrients, regulation of host development, and protection against pathogens. The commensal gut microbiota also constitutively regulates the functional maturation of microglia in the CNS, and microglial function is impaired in its absence in germfree mice. In the current study we determined whether the absence of the commensal gut microbiota might also affect prion disease pathogenesis. Our data clearly show that the absence of the commensal microbiota in germfree mice did not affect prion disease duration or susceptibility after exposure to prions by intraperitoneal or intracerebral injection.
Furthermore, the magnitude and distribution of the characteristic neuropathological hallmarks of terminal prion disease in the CNS, including the development of spongiform pathology, accumulation of prion disease-specific PrP, astrogliosis and microglial activation, were similar in conventionally-housed and germfree mice. Thus although the commensal gut microbiota constitutively promotes the maintenance of the microglia in the CNS under steady-state conditions in naïve mice, our data suggest that dramatic changes to the abundance or complexity of the commensal gut microbiota are unlikely to influence CNS prion disease pathogenesis.