Immobilization stress-induced Escherichia coli causes anxiety by inducing NF-κB activation through gut microbiota disturbance.
Immobilization stress-induced Escherichia coli causes anxiety by inducing NF-κB activation through gut microbiota disturbance.
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DOI：
10.1038/s41598-018-31764-0
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发表时间：
2018-09-17
影响因子：
4.6
通讯作者：
Kim DH
中科院分区：
文献类型：
--
作者：
Jang HM;Lee KE;Lee HJ;Kim DH
本研究旨在了解焦虑与肠道微生物群之间的相互作用。将小鼠暴露于束缚应激（IS）会导致类似焦虑的行为，血液中皮质酮和肿瘤坏死因子 -α水平升高，海马体中核因子（NF）-κB活化以及小胶质细胞/单核细胞数量增加，海马体中脑源性神经营养因子（BDNF）表达受到抑制。此外，IS暴露会增加结肠中NF -κB的活化和单核细胞数量，肠道微生物群以及粪便和血液中变形菌门和大肠杆菌数量增加，脂多糖（LPS）水平升高，同时乳酸杆菌数量减少。口服经IS处理的小鼠粪便微生物群（FIS）或大肠杆菌会导致结肠中NF -κB活化和单核细胞数量增加。这些处理会使血液中皮质酮和LPS水平升高，出现类似焦虑的行为，降低BDNF表达，并诱导海马体中NF -κB活化以及小胶质细胞/单核细胞数量增加。腹腔注射从大肠杆菌中纯化的LPS也会导致小鼠出现焦虑和结肠炎。口服共生乳酸杆菌，特别是约氏乳杆菌，可减轻IS或大肠杆菌诱导的结肠炎和类似焦虑的行为及生物标志物。这些发现表明，暴露于应激源会增加变形菌门数量和粪便LPS水平，并导致胃肠道炎症，通过NF -κB活化使焦虑恶化。然而，通过使用包括约氏乳杆菌在内的益生菌进行治疗来改善胃肠道炎症可以缓解焦虑。
The present study aimed to understand the crosstalk between anxiety and gut microbiota. Exposure of mice to immobilization stress (IS) led to anxiety-like behaviors, increased corticosterone and tumor necrosis factor-α levels in the blood, increased nuclear factor (NF)-κB activation and microglia/monocyte populations in the hippocampus, and suppressed brain-derived neurotrophic factor (BDNF) expression in the hippocampus. Furthermore, IS exposure increased NF-κB activation and monocyte population in the colon and increased Proteobacteria and Escherichia coli populations in the gut microbiota and fecal and blood lipopolysaccharide (LPS) levels while decreasing the lactobacilli population. Oral administration of the fecal microbiota of mice treated with IS (FIS) or E. coli led to the increased NF-κB activation and monocyte population in the colon. These treatments increased blood corticosterone and LPS levels and anxiety-like behaviors, decreased BDNF expression, and induced NF-κB activation and microglia/monocyte populations in the hippocampus. Intraperitoneal injection of LPS purified from E. coli also led to anxiety and colitis in mice. Oral administration of commensal lactobacilli, particularly Lactobacillus johnsonii, attenuated IS- or E. coli-induced colitis and anxiety-like behaviors and biomarkers. These findings suggest that exposure to stressors can increase Proteobacteria populations and fecal LPS levels and cause gastrointestinal inflammation, resulting in the deterioration of anxiety through NF-κB activation. However, the amelioration of gastrointestinal inflammation by treatment with probiotics including L. johnsonii can alleviate anxiety.
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影响因子：
3.7
作者：
Kim KA;Gu W;Lee IA;Joh EH;Kim DH
通讯作者：
Kim DH
影响因子：
56.9
作者：
Gill, Steven R.;Pop, Mihai;Nelson, Karen E.
通讯作者：
Nelson, Karen E.
DOI：
10.1007/978-1-4939-3661-8_16
发表时间：
2016-01-01
期刊：
MOUSE MODELS FOR DRUG DISCOVERY: METHODS AND PROTOCOLS, 2ND EDITION
影响因子：
--
作者：
Hart, Peter C.;Bergner, Carisa L.;Kalueff, Allan V.
通讯作者：
Kalueff, Allan V.
影响因子：
5.4
作者：
Jeong, J. -J.;Kim, K. A.;Kim, D. -H.
通讯作者：
Kim, D. -H.
DOI：
10.1016/j.pnpbp.2012.09.006
发表时间：
2013-01-10
影响因子：
5.6
作者：
Jindal, Ankur;Mahesh, Radhakrishnan;Kumar, Baldev
通讯作者：
Kumar, Baldev