Oral microbiota dysbiosis alters chronic restraint stress-induced depression-like behaviors by modulating host metabolism

作者：Fangzhi Lou, Shihong Luo, Ning Kang, Li Yan, Huiqing Long, Lu Yang, Haiyang Wang, Yiyun Liu, Juncai Pu, Peng Xie, Ping Ji, Xin Jin · 发表于：Pharmacological Research · 年份：2024 · DOI：10.1016/j.phrs.2024.107214 · 被引用次数：26 · 研究领域：Gut microbiota and health、Tryptophan and brain disorders、Salivary Gland Disorders and Functions

Studies have shown that the microbiota-gut-brain axis is highly correlated with the pathogenesis of depression in humans. However, whether independent oral microbiome that do not depend on gut microbes could affect the progression of depression in human beings remains unclear, neither does the presence and underlying mechanisms of the microbiota-oral-brain axis in the development of the condition. Hence this study that encompasses clinical and animal experiments aims at investigating the correlation between oral microbiota and the onset of depression via mediating the microbiota-oral-brain axis. We compared the oral microbial compositions and metabolomes of 87 patients with depressive symptoms versus 70 healthy controls. We found that the oral microbial and metabolic signatures were significantly different between the two groups. Significantly, germ-free (GF) mice transplanted with saliva from mice exposing to chronic restraint stress (CRS) displayed depression-like behavior and oral microbial dysbiosis. This was characterized by a significant differential abundance of bacterial species, including the enrichment of Pseudomonas, Pasteurellaceae, and Muribacter, as well as the depletion of Streptococcus. Metabolomic analysis showed the alternation of metabolites in the plasma of CRS-exposed GF mice, especially Eicosapentaenoic Acid. Furthermore, oral and gut barrier dysfunction caused by CRS-induced oral microbiota dysbiosis may be associated with increased blood-brain barrier ...