Microbiota regulate social behaviour via stress response neurons in the brain

Wei Li Wu, Mark D. Adame, Chia Wei Liou, Jacob T. Barlow, Tzu Ting Lai, Gil Sharon, Catherine E. Schretter, Brittany D. Needham, Madelyn I. Wang, Weiyi Tang, James Ousey, Yuan Yuan Lin, Tzu Hsuan Yao, Reem Abdel-Haq, Keith Beadle, Viviana Gradinaru, Rustem F. Ismagilov, Sarkis K. Mazmanian

研究成果: Article同行評審

摘要

Social interactions among animals mediate essential behaviours, including mating, nurturing, and defence1,2. The gut microbiota contribute to social activity in mice3,4, but the gut–brain connections that regulate this complex behaviour and its underlying neural basis are unclear5,6. Here we show that the microbiome modulates neuronal activity in specific brain regions of male mice to regulate canonical stress responses and social behaviours. Social deviation in germ-free and antibiotic-treated mice is associated with elevated levels of the stress hormone corticosterone, which is primarily produced by activation of the hypothalamus–pituitary–adrenal (HPA) axis. Adrenalectomy, antagonism of glucocorticoid receptors, or pharmacological inhibition of corticosterone synthesis effectively corrects social deficits following microbiome depletion. Genetic ablation of glucocorticoid receptors in specific brain regions or chemogenetic inactivation of neurons in the paraventricular nucleus of the hypothalamus that produce corticotrophin-releasing hormone (CRH) reverse social impairments in antibiotic-treated mice. Conversely, specific activation of CRH-expressing neurons in the paraventricular nucleus induces social deficits in mice with a normal microbiome. Via microbiome profiling and in vivo selection, we identify a bacterial species, Enterococcus faecalis, that promotes social activity and reduces corticosterone levels in mice following social stress. These studies suggest that specific gut bacteria can restrain the activation of the HPA axis, and show that the microbiome can affect social behaviours through discrete neuronal circuits that mediate stress responses in the brain.

原文English
頁(從 - 到)409-414
頁數6
期刊Nature
595
發行號7867
DOIs
出版狀態Published - 2021 七月 15

All Science Journal Classification (ASJC) codes

  • 多學科

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