Microbial disruption in the gut promotes cerebral endothelial dysfunction

Abstract Cerebrovascular disease is a group of conditions characterized by disorders of the cerebral vessels. Endothelial dysfunction renders the vasculature at risk of impaired blood flow and increases the potential of developing cerebrovascular disease. The gut microbiota has been recently identif...

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Autores principales:	April J. Rustia, James S. Paterson, Giles Best, Elke M. Sokoya
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	antibiotics cerebral endothelium microbiota nitric oxide Physiology QP1-981
Acceso en línea:	https://doaj.org/article/75ac19b5633446bea8c0d2764d927c8b
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spelling	oai:doaj.org-article:75ac19b5633446bea8c0d2764d927c8b2021-11-15T09:54:40ZMicrobial disruption in the gut promotes cerebral endothelial dysfunction2051-817X10.14814/phy2.15100https://doaj.org/article/75ac19b5633446bea8c0d2764d927c8b2021-11-01T00:00:00Zhttps://doi.org/10.14814/phy2.15100https://doaj.org/toc/2051-817XAbstract Cerebrovascular disease is a group of conditions characterized by disorders of the cerebral vessels. Endothelial dysfunction renders the vasculature at risk of impaired blood flow and increases the potential of developing cerebrovascular disease. The gut microbiota has been recently identified as a possible risk factor of cerebrovascular disease. However, a direct link between gut microbiota and cerebral vascular function has not been established. Therefore, the aim of this study was to determine the effect of gut bacterial disruption on cerebral endothelial function. Male inbred Sprague‐Dawley rats were randomly assigned to receive either drinking water with (n = 4) or without (n = 4) a cocktail of nonabsorbable broad‐spectrum antibiotics (streptomycin, neomycin, bacitracin, and polymyxin B). Three weeks of antibiotic treatment resulted in a significant reduction in bacterial load and shifts within the bacterial sub‐populations as assessed using flow cytometry. Using pressure myography, we found that spontaneous tone significantly increased and L‐NAME‐induced vasoconstriction was significantly blunted in middle cerebral arteries (MCAs) harvested from antibiotic‐treated rats. ATP‐mediated dilations were significantly blunted in MCAs from antibiotic‐treated rats compared to their control counterparts. Immunoblotting revealed that the eNOS‐P/total eNOS ratio was significantly reduced in cerebral artery lysates from antibiotic‐treated rats compared to controls. Our findings suggest that disruption of the gut microbiota leads to cerebral endothelial dysfunction through reduction of eNOS activity. This study highlights the potential of the microbiota as a target to reverse endothelial dysfunction and a preventative approach to reducing risk of stroke and aneurysms.April J. RustiaJames S. PatersonGiles BestElke M. SokoyaWileyarticleantibioticscerebralendotheliummicrobiotanitric oxidePhysiologyQP1-981ENPhysiological Reports, Vol 9, Iss 21, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	antibiotics cerebral endothelium microbiota nitric oxide Physiology QP1-981
spellingShingle	antibiotics cerebral endothelium microbiota nitric oxide Physiology QP1-981 April J. Rustia James S. Paterson Giles Best Elke M. Sokoya Microbial disruption in the gut promotes cerebral endothelial dysfunction
description	Abstract Cerebrovascular disease is a group of conditions characterized by disorders of the cerebral vessels. Endothelial dysfunction renders the vasculature at risk of impaired blood flow and increases the potential of developing cerebrovascular disease. The gut microbiota has been recently identified as a possible risk factor of cerebrovascular disease. However, a direct link between gut microbiota and cerebral vascular function has not been established. Therefore, the aim of this study was to determine the effect of gut bacterial disruption on cerebral endothelial function. Male inbred Sprague‐Dawley rats were randomly assigned to receive either drinking water with (n = 4) or without (n = 4) a cocktail of nonabsorbable broad‐spectrum antibiotics (streptomycin, neomycin, bacitracin, and polymyxin B). Three weeks of antibiotic treatment resulted in a significant reduction in bacterial load and shifts within the bacterial sub‐populations as assessed using flow cytometry. Using pressure myography, we found that spontaneous tone significantly increased and L‐NAME‐induced vasoconstriction was significantly blunted in middle cerebral arteries (MCAs) harvested from antibiotic‐treated rats. ATP‐mediated dilations were significantly blunted in MCAs from antibiotic‐treated rats compared to their control counterparts. Immunoblotting revealed that the eNOS‐P/total eNOS ratio was significantly reduced in cerebral artery lysates from antibiotic‐treated rats compared to controls. Our findings suggest that disruption of the gut microbiota leads to cerebral endothelial dysfunction through reduction of eNOS activity. This study highlights the potential of the microbiota as a target to reverse endothelial dysfunction and a preventative approach to reducing risk of stroke and aneurysms.
format	article
author	April J. Rustia James S. Paterson Giles Best Elke M. Sokoya
author_facet	April J. Rustia James S. Paterson Giles Best Elke M. Sokoya
author_sort	April J. Rustia
title	Microbial disruption in the gut promotes cerebral endothelial dysfunction
title_short	Microbial disruption in the gut promotes cerebral endothelial dysfunction
title_full	Microbial disruption in the gut promotes cerebral endothelial dysfunction
title_fullStr	Microbial disruption in the gut promotes cerebral endothelial dysfunction
title_full_unstemmed	Microbial disruption in the gut promotes cerebral endothelial dysfunction
title_sort	microbial disruption in the gut promotes cerebral endothelial dysfunction
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/75ac19b5633446bea8c0d2764d927c8b
work_keys_str_mv	AT apriljrustia microbialdisruptioninthegutpromotescerebralendothelialdysfunction AT jamesspaterson microbialdisruptioninthegutpromotescerebralendothelialdysfunction AT gilesbest microbialdisruptioninthegutpromotescerebralendothelialdysfunction AT elkemsokoya microbialdisruptioninthegutpromotescerebralendothelialdysfunction
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Microbial disruption in the gut promotes cerebral endothelial dysfunction

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