Gut commensal Agathobacter rectalis alleviates microglia-mediated neuroinflammation against pathogenesis of Alzheimer disease
Xinhuang Lv,
Lu Zhan,
Tao Ye,
Huijia Xie,
Zhibo Chen,
Yan Lin,
Xianlei Cai,
Wenwen Yang,
Xiaolan Liao,
Jiaming Liu,
Jing Sun
Affiliations
Xinhuang Lv
Department of Geriatrics, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang, China
Lu Zhan
Department of Preventive Medicine, School of Public Health, Wenzhou Medical University, Wenzhou 325027, Zhejiang, China
Tao Ye
Department of Geriatrics, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang, China
Huijia Xie
Department of Geriatrics, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang, China
Zhibo Chen
Department of Neurology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang, China
Yan Lin
Department of Geriatrics, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang, China
Xianlei Cai
Department of Preventive Medicine, School of Public Health, Wenzhou Medical University, Wenzhou 325027, Zhejiang, China
Wenwen Yang
Department of Preventive Medicine, School of Public Health, Wenzhou Medical University, Wenzhou 325027, Zhejiang, China
Xiaolan Liao
Department of Geriatrics, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang, China
Jiaming Liu
Department of Preventive Medicine, School of Public Health, Wenzhou Medical University, Wenzhou 325027, Zhejiang, China; Corresponding author
Jing Sun
Department of Geriatrics, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang, China; Corresponding author
Summary: Gut microbiota plays a crucial role in the pathogenesis of Alzheimer disease (AD). Here, we found that AD patients had significantly lower abundance of Agathobacter, which were negatively correlated with cognitive impairment. Animal experiments showed that Agathobacter rectalis (A. rectalis) supplementation increased beneficial commensal bacteria, significantly improved pathological damage, and suppressed microglial activation in APP/PS1 mice. We further demonstrated that butyric acid, a metabolite of A. rectalis, reduced microglial activation and pro-inflammatory factor production via Akt/ nuclear factor κB (NF-κB) signal pathway in vitro. Meanwhile, we revealed that A. rectalis effectively inhibited activation of microglia in the APP/PS1 mice by regulating Akt/ NF-κB pathway. This finding highlights the role of A. rectalis and its metabolite butyrate in mitigating neuroinflammation in AD by modulating the Akt/NF-κB pathway.
