Although epidemiological studies suggest that
periodontitis is tightly associated with
ischemic stroke, its impact on
ischemic stroke and the underlysing mechanisms are poorly understood. Recent studies have shown that alteration in gut microbiota composition influences the outcomes of
ischemic stroke. In the state of
periodontitis, many oral pathogenic bacteria in the saliva are swallowed and transmitted to the gut. However, the role of
periodontitis microbiota in the pathogenesis and progression of
ischemic stroke is unclear. Therefore, we hypothesized that the
periodontitis salivary microbiota influences the gut immune system and aggravates
ischemic stroke. Mice receiving gavage of
periodontitis salivary microbiota showed significantly worse
stroke outcomes. And these mice also manifested more severe
neuroinflammation, with higher infiltration of inflammatory cells and expression of inflammatory
cytokines in the ischemic brain. More accumulation of Th17 cells and IL-17+ γδ T cells were observed in the ileum. And in Kaede transgenic mice after photoconversion. Migration of CD4+ T cells and γδ T cells from the ileum to the brain was observed after
ischemic stroke in photoconverted Kaede transgenic mice. Furthermore, the worse
stroke outcome was abolished in the
IL-17A knockout mice. These findings suggest that
periodontitis salivary microbiota increased IL-17A-producing immune cells in the gut, likely promoted the migration of these cells from the gut to the brain, and subsequently provoked
neuroinflammation after
ischemic stroke. These findings have revealed the role of
periodontitis in
ischemic stroke through the gut and provided new insights into the worse outcome of
ischemic stroke coexisting with
periodontitis in clinical trials.