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

作者全名：Lou, Fangzhi; Luo, Shihong; Kang, Ning; Yan, Li; Long, Huiqing; Yang, Lu; Wang, Haiyang; Liu, Yiyun; Pu, Juncai; Xie, Peng; Ji, Ping; Jin, Xin

作者地址：[Lou, Fangzhi; Kang, Ning; Long, Huiqing; Yang, Lu; Ji, Ping; Jin, Xin] Chongqing Med Univ, Coll Stomatol, Chongqing 401147, Peoples R China; [Yan, Li] Chongqing Key Lab Oral Dis & Sci, Chongqing 401147, Peoples R China; [Wang, Haiyang; Liu, Yiyun; Pu, Juncai; Xie, Peng] Chongqing Med Univ, Coll Med Informat, Chongqing 400016, Peoples R China; [Jin, Xin] Chongqing Med Univ, Affiliated Hosp 1, NHC Key Lab Diag & Treatment Brain Funct Dis, Chongqing 400042, Peoples R China; [Jin, Xin] Chongqing Med Univ, Stomatol Hosp, 426 Songshi North Rd, Chongqing 401147, Peoples R China

通信作者：Jin, X (通讯作者)，Chongqing Med Univ, Stomatol Hosp, 426 Songshi North Rd, Chongqing 401147, Peoples R China.

来源：PHARMACOLOGICAL RESEARCH

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001244577700001

JCR分区：Q1

影响因子：9.1

年份：2024

卷号：204

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Chronic restraint stress; Depression; Oral microbiota; Gut microbes

摘要：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 depressionlike 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 CRSexposed 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 permeability. Pseudomonas aeruginosa supplementation exacerbated depression-like behavior, while Eicosapentaenoic Acid treatment conferred protection against depression-like states in mice. These results suggest that oral microbiome and metabolic function dysbiosis may be relevant to the pathogenesis and pathophysiology of depression. The proposed microbiota-oral-brain axis provides a new way and targets for us to study the pathogenesis of depression.

基金机构：National Natural Science Foundations of China [82370968]; Natural Science Founda- tion of Chongqing [CSTB2022NSCQ-MSX1148]

基金资助正文：<BOLD>Funding</BOLD> This work was supported by grants from the National Natural Science Foundations of China (No.82370968) and the Natural Science Founda- tion of Chongqing (No. CSTB2022NSCQ-MSX1148) .