Periodontitis-related salivary microbiota aggravates Alzheimer's disease by the crosstalk of gut-brain axis

Increasing evidence has pointed that the periodontitis pathogens and the subsequent inflammatory responses contribute to the pathogenesis of Alzheimer's disease (AD). However, the exact linking mechanisms of periodontitis to AD remain unclear. Oral cavity is the initial part of the digestive tract, and the saliva we swallow per day contains an amount of oral bacteria. The intestine and central nervous system (CNS) engage in crosstalk with each other, and the microbiota-mediated immunity has significant impacts on the AD via the gut-brain axis. Here, we explored the influence of periodontitis salivary microbiota on AD based on the gut brain crosstallk in APP/PS1 (PAP) transgenic mice. The salivary microbiota was collected from patients with periodontitis and healthy individuals and gavaged to the PAP mice for 2 months. The continuous gavage of periodontitis salivary microbiota in PAP mice induced impaired cognitive function, increased beta accumulation and neuroinflammation. What's more, the above AD-related pathologies were consistent with gut microbial dysbiosis, intestinal proinflammatory responses, intestinal barrier impairment, and subsequent exacerbation of systemic inflammation, suggesting that the periodontitis salivary microbiota may aggravate the AD pathogenesis through the gut-brain bidirectional communication. In this study, we demonstrated that periodontitis may participate in the pathogenesis of AD via swallowing salivary microbiota, confirming the role of periodontitis in AD progression and provides a novel perspective on the etiology and intervention strategies of AD.