<i>Porphyromonas gingivalis</i> Induces Disturbance of Kynurenine Metabolism Through the Gut-Brain Axis: Implications for Alzheimer’s Disease

<i>Porphyromonas gingivalis</i> is one of the major pathogens of chronic periodontitis. <i>P. gingivalis</i> can cause systemic inflammation, amyloid β protein deposition, and hyperphosphorylation of tau protein, leading to Alzheimer's disease (AD)-like lesions. <i>P. gingivalis</i> oral infection causes gut microbiota alteration, gut barrier dysfunction, and intestinal immune response and inflammation. The microbiota-gut-brain axis has a potential role in the pathogenesis of AD. Whether <i>P. gingivalis</i> affects AD-like lesions via the gut-brain axis needs more study. In this study, orally administered <i>P. gingivalis</i> induced alveolar resorption, intestinal barrier impairment, and AD-like lesions. Oral infection with <i>P. gingivalis</i> induced oral and gut microflora dysbiosis, imbalance of the tryptophan metabolism pathway of gut microbiota, and elevated levels of 3-hydroxykynurenine in the sera and hippocampi. The key metabolite, 3-hydroxykynurenine, suppressed <i>Bcl2</i> gene expression, leading to neuronal apoptosis and promoting AD-like lesions in vivo and in vitro. These findings suggest that <i>P. gingivalis</i> can induce AD pathogenesis through the gut-brain axis, providing new ideas for the prevention and treatment of AD.