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Inulin supplementation prior to mild traumatic brain injury mitigates gut dysbiosis, and brain vascular and white matter deficits in mice
INTRODUCTION: Mild traumatic brain injury (mTBI) has been shown to negatively alter bacterial diversity and composition within the gut, known as dysbiosis, in rodents and humans. These changes cause secondary consequences systemically through decreased bacterial metabolites such as short chain fatty...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9903356/ https://www.ncbi.nlm.nih.gov/pubmed/36756543 http://dx.doi.org/10.3389/frmbi.2022.986951 |
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author | Yanckello, Lucille M. Chang, Ya-Hsuan Sun, McKenna Chlipala, George Green, Stefan J. Lei, Zhentian Ericsson, Aaron C. Xing, Xin Hammond, Tyler C. Bachstetter, Adam D. Lin, Ai-Ling |
author_facet | Yanckello, Lucille M. Chang, Ya-Hsuan Sun, McKenna Chlipala, George Green, Stefan J. Lei, Zhentian Ericsson, Aaron C. Xing, Xin Hammond, Tyler C. Bachstetter, Adam D. Lin, Ai-Ling |
author_sort | Yanckello, Lucille M. |
collection | PubMed |
description | INTRODUCTION: Mild traumatic brain injury (mTBI) has been shown to negatively alter bacterial diversity and composition within the gut, known as dysbiosis, in rodents and humans. These changes cause secondary consequences systemically through decreased bacterial metabolites such as short chain fatty acids (SCFAs) which play a role in inflammation and metabolism. The goal of the study was to identify if giving prebiotic inulin prior to closed head injury (CHI) could mitigate gut dysbiosis, increase SCFAs, and improve recovery outcomes, including protecting cerebral blood flow (CBF) and white matter integrity (WMI) in young mice. METHODS: We fed mice at 2 months of age with either inulin or control diet (with cellulose as fiber source) for two months before the CHI and continued till the end of the study. We analyzed gut microbiome composition and diversity, determined SCFAs levels, and measured CBF and WMI using MRI. We compared the results with Naïve and Sham-injury mice at 24 hours, 1.5 months, and 3-4 months post-injury. RESULTS: We found that both CHI and Sham mice had time-dependent changes in gut composition and diversity after surgery. Inulin significantly reduced the abundance of pathobiont bacteria, such as E. coli, Desulfovibrio spp and Pseudomonas aeruginosa, in Sham and CHI mice compared to mice fed with control diet. On the other hand, inulin increased SCFAs-producing bacteria, such as Bifidobacterium spp and Lactobacillus spp, increased levels of SCFAs, including butyrate and propionate, and significantly altered beta diversity as early as 24 hours post-injury, which lasted up to 3-4 months post-injury. The mitigation of dysbiosis is associated with protection of WMI in fimbria, internal and external capsule, and CBF in the right hippocampus of CHI mice, suggesting protection of memory and cognitive functions. DISCUSSION: The results indicate that giving inulin prior to CHI could promote recovery outcome through gut microbiome modulation. As inulin, microbiome analysis, and MRI are readily to be used in humans, the findings from the study may pave a way for a cost-effective, accessible intervention for those at risk of sustaining a head injury, such as military personnel or athletes in contact sports. |
format | Online Article Text |
id | pubmed-9903356 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
record_format | MEDLINE/PubMed |
spelling | pubmed-99033562023-02-07 Inulin supplementation prior to mild traumatic brain injury mitigates gut dysbiosis, and brain vascular and white matter deficits in mice Yanckello, Lucille M. Chang, Ya-Hsuan Sun, McKenna Chlipala, George Green, Stefan J. Lei, Zhentian Ericsson, Aaron C. Xing, Xin Hammond, Tyler C. Bachstetter, Adam D. Lin, Ai-Ling Front Microbiomes Article INTRODUCTION: Mild traumatic brain injury (mTBI) has been shown to negatively alter bacterial diversity and composition within the gut, known as dysbiosis, in rodents and humans. These changes cause secondary consequences systemically through decreased bacterial metabolites such as short chain fatty acids (SCFAs) which play a role in inflammation and metabolism. The goal of the study was to identify if giving prebiotic inulin prior to closed head injury (CHI) could mitigate gut dysbiosis, increase SCFAs, and improve recovery outcomes, including protecting cerebral blood flow (CBF) and white matter integrity (WMI) in young mice. METHODS: We fed mice at 2 months of age with either inulin or control diet (with cellulose as fiber source) for two months before the CHI and continued till the end of the study. We analyzed gut microbiome composition and diversity, determined SCFAs levels, and measured CBF and WMI using MRI. We compared the results with Naïve and Sham-injury mice at 24 hours, 1.5 months, and 3-4 months post-injury. RESULTS: We found that both CHI and Sham mice had time-dependent changes in gut composition and diversity after surgery. Inulin significantly reduced the abundance of pathobiont bacteria, such as E. coli, Desulfovibrio spp and Pseudomonas aeruginosa, in Sham and CHI mice compared to mice fed with control diet. On the other hand, inulin increased SCFAs-producing bacteria, such as Bifidobacterium spp and Lactobacillus spp, increased levels of SCFAs, including butyrate and propionate, and significantly altered beta diversity as early as 24 hours post-injury, which lasted up to 3-4 months post-injury. The mitigation of dysbiosis is associated with protection of WMI in fimbria, internal and external capsule, and CBF in the right hippocampus of CHI mice, suggesting protection of memory and cognitive functions. DISCUSSION: The results indicate that giving inulin prior to CHI could promote recovery outcome through gut microbiome modulation. As inulin, microbiome analysis, and MRI are readily to be used in humans, the findings from the study may pave a way for a cost-effective, accessible intervention for those at risk of sustaining a head injury, such as military personnel or athletes in contact sports. 2022 2022-11-30 /pmc/articles/PMC9903356/ /pubmed/36756543 http://dx.doi.org/10.3389/frmbi.2022.986951 Text en 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) (https://creativecommons.org/licenses/by/4.0/) . 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 | Article Yanckello, Lucille M. Chang, Ya-Hsuan Sun, McKenna Chlipala, George Green, Stefan J. Lei, Zhentian Ericsson, Aaron C. Xing, Xin Hammond, Tyler C. Bachstetter, Adam D. Lin, Ai-Ling Inulin supplementation prior to mild traumatic brain injury mitigates gut dysbiosis, and brain vascular and white matter deficits in mice |
title | Inulin supplementation prior to mild traumatic brain injury mitigates gut dysbiosis, and brain vascular and white matter deficits in mice |
title_full | Inulin supplementation prior to mild traumatic brain injury mitigates gut dysbiosis, and brain vascular and white matter deficits in mice |
title_fullStr | Inulin supplementation prior to mild traumatic brain injury mitigates gut dysbiosis, and brain vascular and white matter deficits in mice |
title_full_unstemmed | Inulin supplementation prior to mild traumatic brain injury mitigates gut dysbiosis, and brain vascular and white matter deficits in mice |
title_short | Inulin supplementation prior to mild traumatic brain injury mitigates gut dysbiosis, and brain vascular and white matter deficits in mice |
title_sort | inulin supplementation prior to mild traumatic brain injury mitigates gut dysbiosis, and brain vascular and white matter deficits in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9903356/ https://www.ncbi.nlm.nih.gov/pubmed/36756543 http://dx.doi.org/10.3389/frmbi.2022.986951 |
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