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Short-chain fatty acids mediate gut microbiota-brain communication and protect the blood-brain barrier integrity

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机构: [1]Department of Neurology, West China Hospital, Sichuan University, Chengdu, China. [2]Laboratory of Neurological Disease Modeling and Translational Research, Institute of Neurological Diseases, West China Hospital, Sichuan University, Chengdu, China. [3]State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, China. [4]Guizhou Academy of Testing and Analysis, Guizhou Academy of Sciences, Guiyang, China. [5]Department of Pharmacy, Shaanxi Provincial Cancer Hospital, Xi'an, China. [6]Sichuan Junhui Biotechnology Co., Ltd, Chengdu, China. [7]School of Bioscience and Technology, Chengdu Medical College, Chengdu, China. [8]Sichuan Provincial Center for Mental Health, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
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关键词: antibiotics blood–brain barrier gut microbiome propionate short-chain fatty acids

摘要:
The human gut, with a complex community of microbes, is essential for maintaining overall health. This gut microbiota engages in two-way communication with the central nervous system, collectively known as the gut microbiota-brain axis. Alterations in gut microbiota have been associated with various neurological disorders, and disruptions to the blood-brain barrier (BBB) may be crucial, though the exact mechanisms remain unknown. In the current study, we investigated the impacts of short-chain fatty acids (SCFAs) on the integrity of the BBB, which was compromised by orally administered antibiotics in rhesus monkeys and C57BL/6n mice. Our results showed that SCFA supplementation notably enhanced BBB integrity in rhesus monkeys with gut dysbiosis. Similar outcomes were observed in mice with gut dysbiosis, accompanied by decreased cortical claudin-5 mRNA levels. In particular, propionate, but not acetate or butyrate, could reverse the antibiotic-induced BBB permeability increase in mice. Additionally, in vitro studies demonstrated that propionate boosted the expression of tight junction proteins in brain endothelial cells. These results suggest that the propionate can maintain BBB integrity through a free fatty acid receptor 2-dependent mechanism. This study offers new insights into the gut-brain axis and underscores potential therapeutic targets for interventions based on gut microbiota.© 2025 The New York Academy of Sciences.

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大类 | 3 区 综合性期刊
小类 | 3 区 综合性期刊
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第一作者机构: [1]Department of Neurology, West China Hospital, Sichuan University, Chengdu, China. [2]Laboratory of Neurological Disease Modeling and Translational Research, Institute of Neurological Diseases, West China Hospital, Sichuan University, Chengdu, China. [3]State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, China. [4]Guizhou Academy of Testing and Analysis, Guizhou Academy of Sciences, Guiyang, China.
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通讯机构: [1]Department of Neurology, West China Hospital, Sichuan University, Chengdu, China. [2]Laboratory of Neurological Disease Modeling and Translational Research, Institute of Neurological Diseases, West China Hospital, Sichuan University, Chengdu, China. [3]State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, China. [6]Sichuan Junhui Biotechnology Co., Ltd, Chengdu, China. [8]Sichuan Provincial Center for Mental Health, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
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