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Cefazolin Improves Anesthesia and Surgery-Induced Cognitive Impairments by Modulating Blood-Brain Barrier Function, Gut Bacteria and Short Chain Fatty Acids

Emerging evidence suggests that anesthesia and surgery may induce gut dysbiosis. Gut dysbiosis leads to imbalance in circulating contents of microbiota-derived metabolites and disrupts the integrity of the blood-brain barrier (BBB), contributing to postoperative cognitive dysfunction (POCD). The com...

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Autores principales: Luo, Ailin, Li, Shan, Wang, Xuan, Xie, Zheng, Li, Shiyong, Hua, Dongyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8548472/
https://www.ncbi.nlm.nih.gov/pubmed/34720997
http://dx.doi.org/10.3389/fnagi.2021.748637
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author Luo, Ailin
Li, Shan
Wang, Xuan
Xie, Zheng
Li, Shiyong
Hua, Dongyu
author_facet Luo, Ailin
Li, Shan
Wang, Xuan
Xie, Zheng
Li, Shiyong
Hua, Dongyu
author_sort Luo, Ailin
collection PubMed
description Emerging evidence suggests that anesthesia and surgery may induce gut dysbiosis. Gut dysbiosis leads to imbalance in circulating contents of microbiota-derived metabolites and disrupts the integrity of the blood-brain barrier (BBB), contributing to postoperative cognitive dysfunction (POCD). The composition of gut microbiota may be influenced by various antibiotics. However, how perioperative use of antibiotics affects POCD needs more explorations. In the present study, we explored the effect of cefazolin, a common antibiotic used in perioperative period, on cognitive function, BBB integrity, gut bacteria and short chain fatty acids (SCFAs), a group of widely studied metabolites in aged mice, using 18-month-old male mice. Significant BBB disruptions and decreased levels of tight junction proteins, zonula occludens-1 (ZO-1) and Occludin (OCLN) were seen in the mice of POCD model. Cefazolin treatment attenuated these changes induced by anesthesia and surgery. Furthermore, cefazolin reversed the changes in several fecal bacteria (β-, γ/δ-, ε-Proteobacteria, and Bacteroidetes) as determined by qPCR tests. Analysis of plasma SCFAs showed that almost all types of SCFAs were reduced in POCD and cefazolin administration reversed the changes in expression of the two most abundant SCFAs (acetic and propionic acids). In conclusion, this study demonstrated that cefazolin improved POCD. Mechanistically, cefazolin suppressed the disruption of BBB, gut microbiota or SCFAs, thereby ameliorating POCD.
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spelling pubmed-85484722021-10-28 Cefazolin Improves Anesthesia and Surgery-Induced Cognitive Impairments by Modulating Blood-Brain Barrier Function, Gut Bacteria and Short Chain Fatty Acids Luo, Ailin Li, Shan Wang, Xuan Xie, Zheng Li, Shiyong Hua, Dongyu Front Aging Neurosci Neuroscience Emerging evidence suggests that anesthesia and surgery may induce gut dysbiosis. Gut dysbiosis leads to imbalance in circulating contents of microbiota-derived metabolites and disrupts the integrity of the blood-brain barrier (BBB), contributing to postoperative cognitive dysfunction (POCD). The composition of gut microbiota may be influenced by various antibiotics. However, how perioperative use of antibiotics affects POCD needs more explorations. In the present study, we explored the effect of cefazolin, a common antibiotic used in perioperative period, on cognitive function, BBB integrity, gut bacteria and short chain fatty acids (SCFAs), a group of widely studied metabolites in aged mice, using 18-month-old male mice. Significant BBB disruptions and decreased levels of tight junction proteins, zonula occludens-1 (ZO-1) and Occludin (OCLN) were seen in the mice of POCD model. Cefazolin treatment attenuated these changes induced by anesthesia and surgery. Furthermore, cefazolin reversed the changes in several fecal bacteria (β-, γ/δ-, ε-Proteobacteria, and Bacteroidetes) as determined by qPCR tests. Analysis of plasma SCFAs showed that almost all types of SCFAs were reduced in POCD and cefazolin administration reversed the changes in expression of the two most abundant SCFAs (acetic and propionic acids). In conclusion, this study demonstrated that cefazolin improved POCD. Mechanistically, cefazolin suppressed the disruption of BBB, gut microbiota or SCFAs, thereby ameliorating POCD. Frontiers Media S.A. 2021-10-13 /pmc/articles/PMC8548472/ /pubmed/34720997 http://dx.doi.org/10.3389/fnagi.2021.748637 Text en Copyright © 2021 Luo, Li, Wang, Xie, Li and Hua. 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 Neuroscience
Luo, Ailin
Li, Shan
Wang, Xuan
Xie, Zheng
Li, Shiyong
Hua, Dongyu
Cefazolin Improves Anesthesia and Surgery-Induced Cognitive Impairments by Modulating Blood-Brain Barrier Function, Gut Bacteria and Short Chain Fatty Acids
title Cefazolin Improves Anesthesia and Surgery-Induced Cognitive Impairments by Modulating Blood-Brain Barrier Function, Gut Bacteria and Short Chain Fatty Acids
title_full Cefazolin Improves Anesthesia and Surgery-Induced Cognitive Impairments by Modulating Blood-Brain Barrier Function, Gut Bacteria and Short Chain Fatty Acids
title_fullStr Cefazolin Improves Anesthesia and Surgery-Induced Cognitive Impairments by Modulating Blood-Brain Barrier Function, Gut Bacteria and Short Chain Fatty Acids
title_full_unstemmed Cefazolin Improves Anesthesia and Surgery-Induced Cognitive Impairments by Modulating Blood-Brain Barrier Function, Gut Bacteria and Short Chain Fatty Acids
title_short Cefazolin Improves Anesthesia and Surgery-Induced Cognitive Impairments by Modulating Blood-Brain Barrier Function, Gut Bacteria and Short Chain Fatty Acids
title_sort cefazolin improves anesthesia and surgery-induced cognitive impairments by modulating blood-brain barrier function, gut bacteria and short chain fatty acids
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8548472/
https://www.ncbi.nlm.nih.gov/pubmed/34720997
http://dx.doi.org/10.3389/fnagi.2021.748637
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