Xinru Gu1, Junyi Zhou1, Yanyan Zhou1, Hongjie Wang1, Nan Si1, Wei Ren2, Wei Zhao3, Xiaorui Fan1, Wenya Gao1, Xiaolu Wei1, Jian Yang1, Baolin Bian4, Haiyu Zhao5. 1. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China. 2. Drug Research Center of Integrated Traditional Chinese and Western Medicine, Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, China. 3. Center for Drug Evaluation, National Medical Products Administration, Beijing, 100022, China. 4. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China. blbian@icmm.ac.cn. 5. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China. hyzhao@icmm.ac.cn.
Abstract
BACKGROUND: In recent years, excellent results have suggested an association between the "brain-gut" axis and Alzheimer's disease (AD) progression, yet the role of the "brain-gut" axis in AD pathogenesis still remains obscure. Herein, we provided a potential link between the central and peripheral neuroinflammatory disorders in AD progression. METHODS: The Morris water maze (MWM) test, immunohistochemistry, ELISA, ProcartaPlex Multiplex immunoassay, multiple LC-MS/MS methods, and the V3-V4 regions of 16S rRNA genes were applied to explore potential biomarkers. RESULTS: In Tg-APP/PS1 mice, gut dysbiosis and lipid metabolism were highly associated with AD-like neuroinflammation. The combination of inflammatory factors (IL-6 and INF-γ), phosphatidylcholines (PCs) and SCFA-producing bacteria were expected to be early diagnostic biomarkers for AD. Huanglian Jiedu decoction (HLJDD) suppressed gut dysbiosis and the associated Aβ accumulation, harnessed neuroinflammation and reversed cognitive impairment. CONCLUSION: Together, our findings highlighted the roles of neuroinflammation induced by gut dysbiosis and lipid metabolism disorder in AD progression. This integrated metabolomics approach showed its potential to understand the complex mechanisms of HLJDD in the treatment of AD.
BACKGROUND: In recent years, excellent results have suggested an association between the "brain-gut" axis and Alzheimer's disease (AD) progression, yet the role of the "brain-gut" axis in AD pathogenesis still remains obscure. Herein, we provided a potential link between the central and peripheral neuroinflammatory disorders in AD progression. METHODS: The Morris water maze (MWM) test, immunohistochemistry, ELISA, ProcartaPlex Multiplex immunoassay, multiple LC-MS/MS methods, and the V3-V4 regions of 16S rRNA genes were applied to explore potential biomarkers. RESULTS: In Tg-APP/PS1mice, gut dysbiosis and lipid metabolism were highly associated with AD-like neuroinflammation. The combination of inflammatory factors (IL-6 and INF-γ), phosphatidylcholines (PCs) and SCFA-producing bacteria were expected to be early diagnostic biomarkers for AD. Huanglian Jiedu decoction (HLJDD) suppressed gut dysbiosis and the associated Aβ accumulation, harnessed neuroinflammation and reversed cognitive impairment. CONCLUSION: Together, our findings highlighted the roles of neuroinflammation induced by gut dysbiosis and lipid metabolism disorder in AD progression. This integrated metabolomics approach showed its potential to understand the complex mechanisms of HLJDD in the treatment of AD.
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