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Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer’s disease progression

Recently, increasing evidence has suggested the association between gut dysbiosis and Alzheimer’s disease (AD) progression, yet the role of gut microbiota in AD pathogenesis remains obscure. Herein, we provide a potential mechanistic link between gut microbiota dysbiosis and neuroinflammation in AD...

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Autores principales: Wang, Xinyi, Sun, Guangqiang, Feng, Teng, Zhang, Jing, Huang, Xun, Wang, Tao, Xie, Zuoquan, Chu, Xingkun, Yang, Jun, Wang, Huan, Chang, Shuaishuai, Gong, Yanxue, Ruan, Lingfei, Zhang, Guanqun, Yan, Siyuan, Lian, Wen, Du, Chen, Yang, Dabing, Zhang, Qingli, Lin, Feifei, Liu, Jia, Zhang, Haiyan, Ge, Changrong, Xiao, Shifu, Ding, Jian, Geng, Meiyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6796854/
https://www.ncbi.nlm.nih.gov/pubmed/31488882
http://dx.doi.org/10.1038/s41422-019-0216-x
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author Wang, Xinyi
Sun, Guangqiang
Feng, Teng
Zhang, Jing
Huang, Xun
Wang, Tao
Xie, Zuoquan
Chu, Xingkun
Yang, Jun
Wang, Huan
Chang, Shuaishuai
Gong, Yanxue
Ruan, Lingfei
Zhang, Guanqun
Yan, Siyuan
Lian, Wen
Du, Chen
Yang, Dabing
Zhang, Qingli
Lin, Feifei
Liu, Jia
Zhang, Haiyan
Ge, Changrong
Xiao, Shifu
Ding, Jian
Geng, Meiyu
author_facet Wang, Xinyi
Sun, Guangqiang
Feng, Teng
Zhang, Jing
Huang, Xun
Wang, Tao
Xie, Zuoquan
Chu, Xingkun
Yang, Jun
Wang, Huan
Chang, Shuaishuai
Gong, Yanxue
Ruan, Lingfei
Zhang, Guanqun
Yan, Siyuan
Lian, Wen
Du, Chen
Yang, Dabing
Zhang, Qingli
Lin, Feifei
Liu, Jia
Zhang, Haiyan
Ge, Changrong
Xiao, Shifu
Ding, Jian
Geng, Meiyu
author_sort Wang, Xinyi
collection PubMed
description Recently, increasing evidence has suggested the association between gut dysbiosis and Alzheimer’s disease (AD) progression, yet the role of gut microbiota in AD pathogenesis remains obscure. Herein, we provide a potential mechanistic link between gut microbiota dysbiosis and neuroinflammation in AD progression. Using AD mouse models, we discovered that, during AD progression, the alteration of gut microbiota composition leads to the peripheral accumulation of phenylalanine and isoleucine, which stimulates the differentiation and proliferation of pro-inflammatory T helper 1 (Th1) cells. The brain-infiltrated peripheral Th1 immune cells are associated with the M1 microglia activation, contributing to AD-associated neuroinflammation. Importantly, the elevation of phenylalanine and isoleucine concentrations and the increase of Th1 cell frequency in the blood were also observed in two small independent cohorts of patients with mild cognitive impairment (MCI) due to AD. Furthermore, GV-971, a sodium oligomannate that has demonstrated solid and consistent cognition improvement in a phase 3 clinical trial in China, suppresses gut dysbiosis and the associated phenylalanine/isoleucine accumulation, harnesses neuroinflammation and reverses the cognition impairment. Together, our findings highlight the role of gut dysbiosis-promoted neuroinflammation in AD progression and suggest a novel strategy for AD therapy by remodelling the gut microbiota.
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spelling pubmed-67968542020-01-08 Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer’s disease progression Wang, Xinyi Sun, Guangqiang Feng, Teng Zhang, Jing Huang, Xun Wang, Tao Xie, Zuoquan Chu, Xingkun Yang, Jun Wang, Huan Chang, Shuaishuai Gong, Yanxue Ruan, Lingfei Zhang, Guanqun Yan, Siyuan Lian, Wen Du, Chen Yang, Dabing Zhang, Qingli Lin, Feifei Liu, Jia Zhang, Haiyan Ge, Changrong Xiao, Shifu Ding, Jian Geng, Meiyu Cell Res Article Recently, increasing evidence has suggested the association between gut dysbiosis and Alzheimer’s disease (AD) progression, yet the role of gut microbiota in AD pathogenesis remains obscure. Herein, we provide a potential mechanistic link between gut microbiota dysbiosis and neuroinflammation in AD progression. Using AD mouse models, we discovered that, during AD progression, the alteration of gut microbiota composition leads to the peripheral accumulation of phenylalanine and isoleucine, which stimulates the differentiation and proliferation of pro-inflammatory T helper 1 (Th1) cells. The brain-infiltrated peripheral Th1 immune cells are associated with the M1 microglia activation, contributing to AD-associated neuroinflammation. Importantly, the elevation of phenylalanine and isoleucine concentrations and the increase of Th1 cell frequency in the blood were also observed in two small independent cohorts of patients with mild cognitive impairment (MCI) due to AD. Furthermore, GV-971, a sodium oligomannate that has demonstrated solid and consistent cognition improvement in a phase 3 clinical trial in China, suppresses gut dysbiosis and the associated phenylalanine/isoleucine accumulation, harnesses neuroinflammation and reverses the cognition impairment. Together, our findings highlight the role of gut dysbiosis-promoted neuroinflammation in AD progression and suggest a novel strategy for AD therapy by remodelling the gut microbiota. Nature Publishing Group UK 2019-09-06 2019-10 /pmc/articles/PMC6796854/ /pubmed/31488882 http://dx.doi.org/10.1038/s41422-019-0216-x Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Wang, Xinyi
Sun, Guangqiang
Feng, Teng
Zhang, Jing
Huang, Xun
Wang, Tao
Xie, Zuoquan
Chu, Xingkun
Yang, Jun
Wang, Huan
Chang, Shuaishuai
Gong, Yanxue
Ruan, Lingfei
Zhang, Guanqun
Yan, Siyuan
Lian, Wen
Du, Chen
Yang, Dabing
Zhang, Qingli
Lin, Feifei
Liu, Jia
Zhang, Haiyan
Ge, Changrong
Xiao, Shifu
Ding, Jian
Geng, Meiyu
Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer’s disease progression
title Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer’s disease progression
title_full Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer’s disease progression
title_fullStr Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer’s disease progression
title_full_unstemmed Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer’s disease progression
title_short Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer’s disease progression
title_sort sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit alzheimer’s disease progression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6796854/
https://www.ncbi.nlm.nih.gov/pubmed/31488882
http://dx.doi.org/10.1038/s41422-019-0216-x
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