Gut microbiota of old mice worsens neurological outcome after brain ischemia via increased valeric acid and IL-17 in the blood

Microbiome

Research

Jun Li¹  Weiran Shan¹  Zhongmeng Lai²  Xianzhang Zeng³  Zhiyi Zuo⁴ 

[1] Department of Anesthesiology, University of Virginia, PO Box 800710, 1 Hospital Drive, 22901, Charlottesville, VA, USA;Department of Anesthesiology, University of Virginia, PO Box 800710, 1 Hospital Drive, 22901, Charlottesville, VA, USA;Department of Anesthesiology, Fujian Medical University Union Hospital, 29 Xin-Quan Road, 350001, Fuzhou, People’s Republic of China;Department of Anesthesiology, University of Virginia, PO Box 800710, 1 Hospital Drive, 22901, Charlottesville, VA, USA;Department of Anesthesiology, Second Affiliated Hospital, Harbin Medical University, 150001, Harbin, Heilongjiang, People’s Republic of China;Department of Anesthesiology, University of Virginia, PO Box 800710, 1 Hospital Drive, 22901, Charlottesville, VA, USA;Departments of Neuroscience and Neurosurgery, University of Virginia, 22901, Charlottesville, VA, USA;

关键词: Age;    Focal brain ischemia;    Gut microbiota;    Interleukin-17;    Mice;    Valeric acid;   

DOI  :  10.1186/s40168-023-01648-1

 received in 2023-05-05, accepted in 2023-08-09,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundAging is a significant risk factor for ischemic stroke and worsens its outcome. However, the mechanisms for this worsened neurological outcome with aging are not clearly defined.ResultsOld C57BL/6J male mice (18 to 20 months old) had a poorer neurological outcome and more severe inflammation after transient focal brain ischemia than 8-week-old C57BL/6J male mice (young mice). Young mice with transplantation of old mouse gut microbiota had a worse neurological outcome, poorer survival curve, and more severe inflammation than young mice receiving young mouse gut microbiota transplantation. Old mice and young mice transplanted with old mouse gut microbiota had an increased level of blood valeric acid. Valeric acid worsened neurological outcome and heightened inflammatory response including blood interleukin-17 levels after brain ischemia. The increase of interleukin-17 caused by valeric acid was inhibited by a free fatty acid receptor 2 antagonist. Neutralizing interleukin-17 in the blood by its antibody improved neurological outcome and attenuated inflammatory response in mice with brain ischemia and receiving valeric acid. Old mice transplanted with young mouse feces had less body weight loss and better survival curve after brain ischemia than old mice transplanted with old mouse feces or old mice without fecal transplantation.ConclusionsThese results suggest that the gut microbiota-valeric acid-interleukin-17 pathway contributes to the aging-related changes in the outcome after focal brain ischemia and response to stimulus. Valeric acid may activate free fatty acid receptor 2 to increase interleukin-17.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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