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Modulation of gut microbiota alleviates cerebral ischemia/reperfusion injury in rats by inhibiting M1 polarization of microglia

Gut microbiota affects the gut–brain axis; hence, the modulation of the microbiota has been proposed as a potential therapeutic strategy for cerebral ischemia/reperfusion injury (CIRI). However, the role and mechanism of the gut microbiota in regulating microglial polarization during CIRI remain poo...

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Autores principales: Li, Hai-Jun, Li, Dan-Qing, Zhang, Yu-Liang, Ding, Xiao-Fei, Gao, Hai-Tao, Zhu, Ya, Liu, Jun, Zhang, Li-Xia, Chen, Jie, Chen, Guang, Yu, Ying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10203402/
https://www.ncbi.nlm.nih.gov/pubmed/37229259
http://dx.doi.org/10.3389/fphar.2023.1123387
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author Li, Hai-Jun
Li, Dan-Qing
Zhang, Yu-Liang
Ding, Xiao-Fei
Gao, Hai-Tao
Zhu, Ya
Liu, Jun
Zhang, Li-Xia
Chen, Jie
Chen, Guang
Yu, Ying
author_facet Li, Hai-Jun
Li, Dan-Qing
Zhang, Yu-Liang
Ding, Xiao-Fei
Gao, Hai-Tao
Zhu, Ya
Liu, Jun
Zhang, Li-Xia
Chen, Jie
Chen, Guang
Yu, Ying
author_sort Li, Hai-Jun
collection PubMed
description Gut microbiota affects the gut–brain axis; hence, the modulation of the microbiota has been proposed as a potential therapeutic strategy for cerebral ischemia/reperfusion injury (CIRI). However, the role and mechanism of the gut microbiota in regulating microglial polarization during CIRI remain poorly understood. Herein, using a middle cerebral artery occlusion and reperfusion (MCAO/R) rat model, we evaluated changes in the gut microbiota after CIRI and the potential effects of fecal microbiota transplant (FMT) on the brain. Rats underwent either MCAO/R or sham surgery, and then they received FMT (started 3 days later; continued for 10 days). 2,3,5-Triphenyltetrazolium chloride staining, neurological outcome scale, and Fluoro-Jade C staining showed that MCAO/R induced cerebral infarction, neurological deficits, and neuronal degeneration. In addition, immunohistochemistry or real-time PCR assay showed increased expression levels of M1-macrophage markers—TNF-α, IL-1β, IL-6, and iNOS—in the rats following MCAO/R. Our finding suggests that microglial M1 polarization is involved in CIRI. 16 S ribosomal RNA gene sequencing data revealed an imbalance in the gut microbiota of MCAO/R animals. In contrast, FMT reversed this MCAO/R-induced imbalance in the gut microbiota and ameliorated nerve injury. In addition, FMT prevented the upregulation in the ERK and NF-κB pathways, which reversed the M2-to-M1 microglial shift 10 days after MCAO/R injury in rats. Our primary data showed that the modulation of the gut microbiota can attenuate CIRI in rats by inhibiting microglial M1 polarization through the ERK and NF-κB pathways. However, an understanding of the underlying mechanism requires further study.
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spelling pubmed-102034022023-05-24 Modulation of gut microbiota alleviates cerebral ischemia/reperfusion injury in rats by inhibiting M1 polarization of microglia Li, Hai-Jun Li, Dan-Qing Zhang, Yu-Liang Ding, Xiao-Fei Gao, Hai-Tao Zhu, Ya Liu, Jun Zhang, Li-Xia Chen, Jie Chen, Guang Yu, Ying Front Pharmacol Pharmacology Gut microbiota affects the gut–brain axis; hence, the modulation of the microbiota has been proposed as a potential therapeutic strategy for cerebral ischemia/reperfusion injury (CIRI). However, the role and mechanism of the gut microbiota in regulating microglial polarization during CIRI remain poorly understood. Herein, using a middle cerebral artery occlusion and reperfusion (MCAO/R) rat model, we evaluated changes in the gut microbiota after CIRI and the potential effects of fecal microbiota transplant (FMT) on the brain. Rats underwent either MCAO/R or sham surgery, and then they received FMT (started 3 days later; continued for 10 days). 2,3,5-Triphenyltetrazolium chloride staining, neurological outcome scale, and Fluoro-Jade C staining showed that MCAO/R induced cerebral infarction, neurological deficits, and neuronal degeneration. In addition, immunohistochemistry or real-time PCR assay showed increased expression levels of M1-macrophage markers—TNF-α, IL-1β, IL-6, and iNOS—in the rats following MCAO/R. Our finding suggests that microglial M1 polarization is involved in CIRI. 16 S ribosomal RNA gene sequencing data revealed an imbalance in the gut microbiota of MCAO/R animals. In contrast, FMT reversed this MCAO/R-induced imbalance in the gut microbiota and ameliorated nerve injury. In addition, FMT prevented the upregulation in the ERK and NF-κB pathways, which reversed the M2-to-M1 microglial shift 10 days after MCAO/R injury in rats. Our primary data showed that the modulation of the gut microbiota can attenuate CIRI in rats by inhibiting microglial M1 polarization through the ERK and NF-κB pathways. However, an understanding of the underlying mechanism requires further study. Frontiers Media S.A. 2023-05-09 /pmc/articles/PMC10203402/ /pubmed/37229259 http://dx.doi.org/10.3389/fphar.2023.1123387 Text en Copyright © 2023 Li, Li, Zhang, Ding, Gao, Zhu, Liu, Zhang, Chen, Chen and Yu. https://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 Pharmacology
Li, Hai-Jun
Li, Dan-Qing
Zhang, Yu-Liang
Ding, Xiao-Fei
Gao, Hai-Tao
Zhu, Ya
Liu, Jun
Zhang, Li-Xia
Chen, Jie
Chen, Guang
Yu, Ying
Modulation of gut microbiota alleviates cerebral ischemia/reperfusion injury in rats by inhibiting M1 polarization of microglia
title Modulation of gut microbiota alleviates cerebral ischemia/reperfusion injury in rats by inhibiting M1 polarization of microglia
title_full Modulation of gut microbiota alleviates cerebral ischemia/reperfusion injury in rats by inhibiting M1 polarization of microglia
title_fullStr Modulation of gut microbiota alleviates cerebral ischemia/reperfusion injury in rats by inhibiting M1 polarization of microglia
title_full_unstemmed Modulation of gut microbiota alleviates cerebral ischemia/reperfusion injury in rats by inhibiting M1 polarization of microglia
title_short Modulation of gut microbiota alleviates cerebral ischemia/reperfusion injury in rats by inhibiting M1 polarization of microglia
title_sort modulation of gut microbiota alleviates cerebral ischemia/reperfusion injury in rats by inhibiting m1 polarization of microglia
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10203402/
https://www.ncbi.nlm.nih.gov/pubmed/37229259
http://dx.doi.org/10.3389/fphar.2023.1123387
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