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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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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. |
format | Online Article Text |
id | pubmed-6796854 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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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