The gut–brain axis is a bidirectional communication system between the gut and central nervous system. Many host-related factors can affect gut microbiota, including oral bacteria, making the brain a vulnerable target via the gut–brain axis. Saliva contains a large number of oral bacteria, and periodontitis, a common oral disease, can change the composition of salivary microbiota. However, the role and mechanism of periodontitis salivary microbiota (PSM) on the gut–brain axis remain unclear. Herein, we investigated the nature and mechanisms of this relationship using the mice with dextran sulfate sodium salt (DSS)-induced anxiety-like behavior. Compared with healthy salivary microbiota, PSM worsened anxiety-like behavior; it significantly reduced the number of normal neurons and activated microglia in DSS mice. Antibiotic treatment eliminated the effect of PSM on anxiety-like behavior, and transplantation of fecal microbiota from PSM-gavaged mice exacerbated anxiety-like behavior. These observations indicated that the anxiety-exacerbating effect of PSM was dependent on the gut microbiota. Moreover, the PSM effect on anxiety-like behavior was not present in non-DSS mice, indicating that DSS treatment was a prerequisite for PSM to exacerbate anxiety. Mechanistically, PSM altered the histidine metabolism in both gut and brain metabolomics. Supplementation of histidine-related metabolites had a similar anxiety-exacerbating effect as that of PSM, suggesting that histidine metabolism may be a critical pathway in this process. Our results demonstrate that PSM can exacerbate colitis-induced anxiety-like behavior by directly affecting the host gut microbiota, emphasizing the importance of oral diseases in the gut–brain axis.

肠脑轴是肠道和中枢神经系统之间的双向通讯系统。许多与宿主相关的因素都会影响肠道微生物群，包括口腔细菌，使大脑成为肠脑轴的脆弱目标。唾液中含有大量口腔细菌，牙周炎这种常见的口腔疾病会改变唾液微生物群的组成。然而，牙周炎唾液微生物群（PSM）对肠-脑轴的作用和机制仍不清楚。在此，我们使用右旋糖酐硫酸钠盐（DSS）诱导的焦虑样行为的小鼠研究了这种关系的性质和机制。与健康唾液微生物群相比，PSM 使焦虑样行为恶化；它显着减少了 DSS 小鼠正常神经元的数量并激活了小胶质细胞。抗生素治疗消除了 PSM 对焦虑样行为的影响，而移植 PSM 灌胃小鼠的粪便微生物群则加剧了焦虑样行为。这些观察结果表明，PSM 的焦虑加剧作用取决于肠道微生物群。此外，PSM 对焦虑样行为的影响在非 DSS 小鼠中不存在，表明 DSS 治疗是 PSM 加剧焦虑的先决条件。从机制上讲，PSM 改变了肠道和大脑代谢组学中的组氨酸代谢。补充组氨酸相关代谢物与 PSM 具有类似的焦虑加剧作用，表明组氨酸代谢可能是这一过程中的关键途径。我们的结果表明，PSM 可以通过直接影响宿主肠道微生物群来加剧结肠炎引起的焦虑样行为，强调了口腔疾病在肠脑轴中的重要性。