Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Co-toxicity of Endotoxin and Indoxyl Sulfate, Gut-Derived Bacterial Metabolites, to Vascular Endothelial Cells in Coronary Arterial Disease Accompanied by Gut Dysbiosis

Marcin Choroszy
,
Beata Sobieszczanska
* ,
Kamil Litwinowicz
,
Lukasz Laczmanski
ORCID logo ,
Mateusz Chmielarz
,
Urszula Walczuk
,
Tomasz Roleder
,
Jadwiga Radziejewska
,
Magdalena Wawrzyńska
Version 1 : Received: 29 September 2021 / Approved: 5 October 2021 / Online: 5 October 2021 (10:33:24 CEST)

How to cite: Choroszy, M.; Sobieszczanska, B.; Litwinowicz, K.; Laczmanski, L.; Chmielarz, M.; Walczuk, U.; Roleder, T.; Radziejewska, J.; Wawrzyńska, M. Co-toxicity of Endotoxin and Indoxyl Sulfate, Gut-Derived Bacterial Metabolites, to Vascular Endothelial Cells in Coronary Arterial Disease Accompanied by Gut Dysbiosis. Preprints 2021, 2021100076. https://doi.org/10.20944/preprints202110.0076.v1 Choroszy, M.; Sobieszczanska, B.; Litwinowicz, K.; Laczmanski, L.; Chmielarz, M.; Walczuk, U.; Roleder, T.; Radziejewska, J.; Wawrzyńska, M. Co-toxicity of Endotoxin and Indoxyl Sulfate, Gut-Derived Bacterial Metabolites, to Vascular Endothelial Cells in Coronary Arterial Disease Accompanied by Gut Dysbiosis. Preprints 2021, 2021100076. https://doi.org/10.20944/preprints202110.0076.v1

Abstract

Gut dysbiosis, alongside with high-fat diet and cigarette smoking, is considered one of the factors promoting coronary arterial disease (CAD) development. The present study aimed to research whether gut dysbiosis can increase bacterial metabolites concentration in the blood of CAD patients and what impact these metabolites can exert on endothelial cells. The gut microbiome of 15 CAD patients and age-matched 15 healthy controls was analyzed by metagenome sequencing. The in vitro impact of LPS and indoxyl sulfate at concentrations present in patients sera on endothelial cells was investigated. A metagenome sequencing analysis revealed gut dysbiosis in CAD patients, further confirmed by elevated levels of LPS and indoxyl sulfate in patients sera. CAD was associated with depletion of Bacteroidetes and Alistipes. LPS and indoxyl sulfate in meager concentrations demonstrated co-toxicity to endothelial cells inducing reactive oxygen species, E-selectin, and monocyte chemoattractant protein-1 (MCP-1) production and promoting thrombogenicity of endothelial cells confirmed by monocyte adherence. The co-toxicity of LPS and indoxyl sulfate was associated with harmful effects on endothelial cells, strongly suggesting that gut dysbiosis-associated increased intestinal permeability can initiate or promote endothelial inflammation and atherosclerosis progression.

Keywords

coronary artery disease; gut microbiome; dysbiosis; obesity; Bacteroidetes; LPS; indoxyl sulfate

Subject

Medicine and Pharmacology, Cardiac and Cardiovascular Systems

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Download PDF Download Supplementary

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0
Get PDF Supplementary Files Cite Share 0
Bookmark BibSonomy Mendeley Reddit Delicious
×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.