Prevotella intermedia oral infection induces cognitive impairment in C57BL/6 mice via neuroinflammation and barrier damage.

BACKGROUND

Oral pathogens play a significant role in the pathogenesis of Alzheimer's disease (AD) via the oral-brain axis and oral-gut-brain axis. However, how Prevotella intermedia (P. intermedia) affect the development of AD remains unclear.

OBJECTIVE

To investigate the effects of P. intermedia infection on neuroinflammation and cognitive function.

DESIGN

Sixty C57BL/6 mice were divided into two cohorts and infected with P. intermedia via gingival injection or oral gavage, mimicking pathogen invasion. The microbiota changes of saliva collected from 5 AD patients and 5 healthy individuals were analyzed by 16S rRNA sequencing.

RESULTS

Gingival injection resulted in cognitive impairment, neuronal loss in the hippocampal CA1/CA3 regions (p < 0.05), overactivation of microglia and increased expression of proinflammatory cytokines (IL-1β and TNF-α, p < 0.05) and NF-κB in hippocampus (p < 0.05). Similar cognitive impairments and cerebral changes were noted after oral gavaging. Additionally, oral gavage induced gut microbiota dysbiosis, intestinal inflammation and decreased expression of tight junction in intestinal barrier and blood-brain barrier (ZO-1, Occludin, Claudin-1 and Claudin-5, p < 0.05). Furthermore, AD patients exhibited oral microbiota dysbiosis, with a higher relative abundance of P. intermedia (p < 0.05).

CONCLUSION

P. intermedia is associated with cognitive impairment and AD-related neuroinflammation via the oral-brain and oral-gut-brain axes.