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Persistence of Gut Microbiota Dysbiosis and Chronic Systemic Inflammation After Cerebral Infarction in Cynomolgus Monkeys

Background: The bidirectional interaction between the gut and brain after stroke through the immune-mediated pathway has been studied. However, the long-term effects of gut microbiota and systemic immune homeostasis after cerebral ischemia remain unclear. We examined long-term changes in the gut mic...

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Autores principales: Chen, Yonghong, Liang, Jiahui, Ouyang, Fubing, Chen, Xinran, Lu, Tao, Jiang, Zimu, Li, Jianle, Li, Yuefeng, Zeng, Jinsheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6611357/
https://www.ncbi.nlm.nih.gov/pubmed/31316450
http://dx.doi.org/10.3389/fneur.2019.00661
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author Chen, Yonghong
Liang, Jiahui
Ouyang, Fubing
Chen, Xinran
Lu, Tao
Jiang, Zimu
Li, Jianle
Li, Yuefeng
Zeng, Jinsheng
author_facet Chen, Yonghong
Liang, Jiahui
Ouyang, Fubing
Chen, Xinran
Lu, Tao
Jiang, Zimu
Li, Jianle
Li, Yuefeng
Zeng, Jinsheng
author_sort Chen, Yonghong
collection PubMed
description Background: The bidirectional interaction between the gut and brain after stroke through the immune-mediated pathway has been studied. However, the long-term effects of gut microbiota and systemic immune homeostasis after cerebral ischemia remain unclear. We examined long-term changes in the gut microbiota and systemic inflammatory cytokines after cerebral infarction in cynomolgus monkeys. Methods: Twelve monkeys underwent successful distal M1 segment of the left middle cerebral artery occlusion (MCAO) and were randomly and equally assigned to the MCAO-1.5 m, MCAO-6 m, and MCAO-12 m groups, which were sacrificed 1.5, 6, and 12 months after cerebral infarction induction, respectively. Four monkeys that underwent a sham operation were sacrificed 12 months later. The gut microbiota and short-chain fatty acids (SCFAs) were analyzed by 16S rDNA sequencing and gas chromatography mass spectrometry, respectively. Histological examinations of the transverse colon were performed. Plasma D-lactate, zonulin, lipopolysaccharide (LPS), tumor necrosis factor (TNF-α), interferon (IFN)-γ, and interleukin (IL)-6 were detected by immunoassay kits. Results: The levels of the Bacteroidetes phylum and Prevotella genus were significantly increased, while the Firmicutes phylum as well as the Faecalibacterium, Oscillospira, and Lactobacillus genera were decreased after cerebral infarction. Gut-originating SCFAs were significantly decreased 6 and 12 months after cerebral infarction (P < 0.05). We observed intestinal mucosal damage, evaluated by Chiu's score. Plasma D-lactate, zonulin, LPS, TNF-α, IFN-γ, and IL-6 were significantly increased after cerebral infarction (P < 0.05). Additionally, the increases in plasma LPS, TNF-α, IFN-γ, and IL-6 after cerebral infarction coincided with overgrowth of the Bacteroidetes phylum (P < 0.001). Conclusion: Cerebral infarction induces persistent host gut microbiota dysbiosis, intestinal mucosal damage, and chronic systemic inflammation in cynomolgus monkeys.
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spelling pubmed-66113572019-07-17 Persistence of Gut Microbiota Dysbiosis and Chronic Systemic Inflammation After Cerebral Infarction in Cynomolgus Monkeys Chen, Yonghong Liang, Jiahui Ouyang, Fubing Chen, Xinran Lu, Tao Jiang, Zimu Li, Jianle Li, Yuefeng Zeng, Jinsheng Front Neurol Neurology Background: The bidirectional interaction between the gut and brain after stroke through the immune-mediated pathway has been studied. However, the long-term effects of gut microbiota and systemic immune homeostasis after cerebral ischemia remain unclear. We examined long-term changes in the gut microbiota and systemic inflammatory cytokines after cerebral infarction in cynomolgus monkeys. Methods: Twelve monkeys underwent successful distal M1 segment of the left middle cerebral artery occlusion (MCAO) and were randomly and equally assigned to the MCAO-1.5 m, MCAO-6 m, and MCAO-12 m groups, which were sacrificed 1.5, 6, and 12 months after cerebral infarction induction, respectively. Four monkeys that underwent a sham operation were sacrificed 12 months later. The gut microbiota and short-chain fatty acids (SCFAs) were analyzed by 16S rDNA sequencing and gas chromatography mass spectrometry, respectively. Histological examinations of the transverse colon were performed. Plasma D-lactate, zonulin, lipopolysaccharide (LPS), tumor necrosis factor (TNF-α), interferon (IFN)-γ, and interleukin (IL)-6 were detected by immunoassay kits. Results: The levels of the Bacteroidetes phylum and Prevotella genus were significantly increased, while the Firmicutes phylum as well as the Faecalibacterium, Oscillospira, and Lactobacillus genera were decreased after cerebral infarction. Gut-originating SCFAs were significantly decreased 6 and 12 months after cerebral infarction (P < 0.05). We observed intestinal mucosal damage, evaluated by Chiu's score. Plasma D-lactate, zonulin, LPS, TNF-α, IFN-γ, and IL-6 were significantly increased after cerebral infarction (P < 0.05). Additionally, the increases in plasma LPS, TNF-α, IFN-γ, and IL-6 after cerebral infarction coincided with overgrowth of the Bacteroidetes phylum (P < 0.001). Conclusion: Cerebral infarction induces persistent host gut microbiota dysbiosis, intestinal mucosal damage, and chronic systemic inflammation in cynomolgus monkeys. Frontiers Media S.A. 2019-06-28 /pmc/articles/PMC6611357/ /pubmed/31316450 http://dx.doi.org/10.3389/fneur.2019.00661 Text en Copyright © 2019 Chen, Liang, Ouyang, Chen, Lu, Jiang, Li, Li and Zeng. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neurology
Chen, Yonghong
Liang, Jiahui
Ouyang, Fubing
Chen, Xinran
Lu, Tao
Jiang, Zimu
Li, Jianle
Li, Yuefeng
Zeng, Jinsheng
Persistence of Gut Microbiota Dysbiosis and Chronic Systemic Inflammation After Cerebral Infarction in Cynomolgus Monkeys
title Persistence of Gut Microbiota Dysbiosis and Chronic Systemic Inflammation After Cerebral Infarction in Cynomolgus Monkeys
title_full Persistence of Gut Microbiota Dysbiosis and Chronic Systemic Inflammation After Cerebral Infarction in Cynomolgus Monkeys
title_fullStr Persistence of Gut Microbiota Dysbiosis and Chronic Systemic Inflammation After Cerebral Infarction in Cynomolgus Monkeys
title_full_unstemmed Persistence of Gut Microbiota Dysbiosis and Chronic Systemic Inflammation After Cerebral Infarction in Cynomolgus Monkeys
title_short Persistence of Gut Microbiota Dysbiosis and Chronic Systemic Inflammation After Cerebral Infarction in Cynomolgus Monkeys
title_sort persistence of gut microbiota dysbiosis and chronic systemic inflammation after cerebral infarction in cynomolgus monkeys
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6611357/
https://www.ncbi.nlm.nih.gov/pubmed/31316450
http://dx.doi.org/10.3389/fneur.2019.00661
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