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Sodium butyrate mediates histone crotonylation and alleviated neonatal rats hypoxic–ischemic brain injury through gut–brain axis

Neonatal hypoxic–ischemic encephalopathy (HIE) refers to nervous system damage caused by perinatal hypoxia, which is the major cause of long-term neuro-developmental disorders in surviving infants. However, the mechanisms still require further investigation. In this study, we found that the butanoat...

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Autores principales: He, Xuejia, Zhang, Ting, Zeng, Yubing, Pei, Pei, Liu, Yulan, Jia, Wenbin, Zhao, Hongyang, Bi, Meirong, Wang, Shan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9631217/
https://www.ncbi.nlm.nih.gov/pubmed/36338029
http://dx.doi.org/10.3389/fmicb.2022.993146
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author He, Xuejia
Zhang, Ting
Zeng, Yubing
Pei, Pei
Liu, Yulan
Jia, Wenbin
Zhao, Hongyang
Bi, Meirong
Wang, Shan
author_facet He, Xuejia
Zhang, Ting
Zeng, Yubing
Pei, Pei
Liu, Yulan
Jia, Wenbin
Zhao, Hongyang
Bi, Meirong
Wang, Shan
author_sort He, Xuejia
collection PubMed
description Neonatal hypoxic–ischemic encephalopathy (HIE) refers to nervous system damage caused by perinatal hypoxia, which is the major cause of long-term neuro-developmental disorders in surviving infants. However, the mechanisms still require further investigation. In this study, we found that the butanoate metabolism pathway exhibited significantly decreased and short chain fatty acid (SCFAs)-producing bacteria, especially butyrate-producing bacteria, were significantly decreased in fecal of neonatal hypoxic–ischemic brain damage (HIBD) rats. Surprisingly, Sodium butyrate (SB) treatment could ameliorate pathological damage both in the cerebral cortex and hippocampus and facilitate recovery of SCFAs-producing bacteria related to metabolic pathways in neonatal HIBD rats. Moreover, we found that in samples from SB treatment neonatal HIBD rats cortex with high levels of butyrate acid along with aberrant key crotonyl-CoA-producing enzymes ACADS levels were observed compared HIBD rats. We also demonstrated that a decrease in histone 3-lysine 9-crotonylation (H3K9cr) downregulated expression of the HIE-related neurotrophic genes Bdnf, Gdnf, Cdnf, and Manf in HIBD rats. Furthermore, SB restored H3K9cr binding to HIE-related neurotrophic genes. Collectively, our results indicate that SB contributes to ameliorate pathology of HIBD by altering gut microbiota and brain SCFAs levels subsequently affecting histone crotonylation-mediated neurotrophic-related genes expression. This may be a novel microbiological approach for preventing and treating HIE.
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spelling pubmed-96312172022-11-04 Sodium butyrate mediates histone crotonylation and alleviated neonatal rats hypoxic–ischemic brain injury through gut–brain axis He, Xuejia Zhang, Ting Zeng, Yubing Pei, Pei Liu, Yulan Jia, Wenbin Zhao, Hongyang Bi, Meirong Wang, Shan Front Microbiol Microbiology Neonatal hypoxic–ischemic encephalopathy (HIE) refers to nervous system damage caused by perinatal hypoxia, which is the major cause of long-term neuro-developmental disorders in surviving infants. However, the mechanisms still require further investigation. In this study, we found that the butanoate metabolism pathway exhibited significantly decreased and short chain fatty acid (SCFAs)-producing bacteria, especially butyrate-producing bacteria, were significantly decreased in fecal of neonatal hypoxic–ischemic brain damage (HIBD) rats. Surprisingly, Sodium butyrate (SB) treatment could ameliorate pathological damage both in the cerebral cortex and hippocampus and facilitate recovery of SCFAs-producing bacteria related to metabolic pathways in neonatal HIBD rats. Moreover, we found that in samples from SB treatment neonatal HIBD rats cortex with high levels of butyrate acid along with aberrant key crotonyl-CoA-producing enzymes ACADS levels were observed compared HIBD rats. We also demonstrated that a decrease in histone 3-lysine 9-crotonylation (H3K9cr) downregulated expression of the HIE-related neurotrophic genes Bdnf, Gdnf, Cdnf, and Manf in HIBD rats. Furthermore, SB restored H3K9cr binding to HIE-related neurotrophic genes. Collectively, our results indicate that SB contributes to ameliorate pathology of HIBD by altering gut microbiota and brain SCFAs levels subsequently affecting histone crotonylation-mediated neurotrophic-related genes expression. This may be a novel microbiological approach for preventing and treating HIE. Frontiers Media S.A. 2022-10-20 /pmc/articles/PMC9631217/ /pubmed/36338029 http://dx.doi.org/10.3389/fmicb.2022.993146 Text en Copyright © 2022 He, Zhang, Zeng, Pei, Liu, Jia, Zhao, Bi and Wang. 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 Microbiology
He, Xuejia
Zhang, Ting
Zeng, Yubing
Pei, Pei
Liu, Yulan
Jia, Wenbin
Zhao, Hongyang
Bi, Meirong
Wang, Shan
Sodium butyrate mediates histone crotonylation and alleviated neonatal rats hypoxic–ischemic brain injury through gut–brain axis
title Sodium butyrate mediates histone crotonylation and alleviated neonatal rats hypoxic–ischemic brain injury through gut–brain axis
title_full Sodium butyrate mediates histone crotonylation and alleviated neonatal rats hypoxic–ischemic brain injury through gut–brain axis
title_fullStr Sodium butyrate mediates histone crotonylation and alleviated neonatal rats hypoxic–ischemic brain injury through gut–brain axis
title_full_unstemmed Sodium butyrate mediates histone crotonylation and alleviated neonatal rats hypoxic–ischemic brain injury through gut–brain axis
title_short Sodium butyrate mediates histone crotonylation and alleviated neonatal rats hypoxic–ischemic brain injury through gut–brain axis
title_sort sodium butyrate mediates histone crotonylation and alleviated neonatal rats hypoxic–ischemic brain injury through gut–brain axis
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9631217/
https://www.ncbi.nlm.nih.gov/pubmed/36338029
http://dx.doi.org/10.3389/fmicb.2022.993146
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