PMID- 35276782 OWN - NLM STAT- MEDLINE DCOM- 20220315 LR - 20220315 IS - 2072-6643 (Electronic) IS - 2072-6643 (Linking) VI - 14 IP - 3 DP - 2022 Jan 18 TI - Co-toxicity of Endotoxin and Indoxyl Sulfate, Gut-Derived Bacterial Metabolites, to Vascular Endothelial Cells in Coronary Arterial Disease Accompanied by Gut Dysbiosis. LID - 10.3390/nu14030424 [doi] LID - 424 AB - Gut dysbiosis, alongside a 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 microbiomes of 15 age-matched CAD patients and healthy controls were analyzed by 16S rRNA sequencing analysis. The in vitro impact of LPS and indoxyl sulfate at concentrations present in patients' sera on endothelial cells was investigated. 16S rRNA sequencing analysis revealed gut dysbiosis in CAD patients, further confirmed by elevated LPS and indoxyl sulfate levels in patients' sera. CAD was associated with depletion of Bacteroidetes and Alistipes. LPS and indoxyl sulfate demonstrated co-toxicity to endothelial cells inducing reactive oxygen species, E-selectin, and monocyte chemoattractant protein-1 (MCP-1) production. Moreover, both of these metabolites promoted 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. FAU - Choroszy, Marcin AU - Choroszy M AD - Department of Microbiology, Wroclaw Medical University, Chalubinskiego 4 Street, 51-657 Wroclaw, Poland. FAU - Sobieszczanska, Beata AU - Sobieszczanska B AD - Department of Microbiology, Wroclaw Medical University, Chalubinskiego 4 Street, 51-657 Wroclaw, Poland. FAU - Litwinowicz, Kamil AU - Litwinowicz K AD - Department of Medical Biochemistry, Wroclaw Medical University, Chalubinskiego 10 Street, 50-368 Wroclaw, Poland. FAU - Laczmanski, Lukasz AU - Laczmanski L AUID- ORCID: 0000-0002-0874-5483 AD - Laboratory of Genomics & Bioinformatics, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12 Street, 53-114 Wroclaw, Poland. FAU - Chmielarz, Mateusz AU - Chmielarz M AUID- ORCID: 0000-0002-5364-6556 AD - Department of Microbiology, Wroclaw Medical University, Chalubinskiego 4 Street, 51-657 Wroclaw, Poland. FAU - Walczuk, Urszula AU - Walczuk U AUID- ORCID: 0000-0002-4344-9882 AD - Department of Microbiology, Wroclaw Medical University, Chalubinskiego 4 Street, 51-657 Wroclaw, Poland. FAU - Roleder, Tomasz AU - Roleder T AD - Research and Development Centre, Regional Specialist Hospital, Kamienskiego 73a Street, 51-124 Wroclaw, Poland. FAU - Radziejewska, Jadwiga AU - Radziejewska J AD - Klodzko County Hospital, 57-300 Klodzko, Poland. FAU - Wawrzynska, Magdalena AU - Wawrzynska M AD - Department of Preclinical Studies, Faculty of Health Sciences, Wroclaw Medical University, 50-367 Wroclaw, Poland. LA - eng GR - STM.A130.20.158/Wroclaw Medical University, Poland/ PT - Journal Article DEP - 20220118 PL - Switzerland TA - Nutrients JT - Nutrients JID - 101521595 RN - 0 (Endotoxins) RN - 0 (RNA, Ribosomal, 16S) RN - N187WK1Y1J (Indican) SB - IM MH - *Dysbiosis/microbiology MH - Endothelial Cells MH - Endotoxins MH - Humans MH - *Indican/toxicity MH - RNA, Ribosomal, 16S/genetics PMC - PMC8840142 OTO - NOTNLM OT - Bacteroidetes OT - LPS OT - coronary artery disease OT - dysbiosis OT - gut microbiome OT - indoxyl sulfate OT - obesity COIS- The authors declare no known competing financial interests or personal relationships that could influence the work reported in this paper. EDAT- 2022/03/13 06:00 MHDA- 2022/03/16 06:00 PMCR- 2022/01/18 CRDT- 2022/03/12 01:00 PHST- 2021/11/15 00:00 [received] PHST- 2022/01/10 00:00 [revised] PHST- 2022/01/13 00:00 [accepted] PHST- 2022/03/12 01:00 [entrez] PHST- 2022/03/13 06:00 [pubmed] PHST- 2022/03/16 06:00 [medline] PHST- 2022/01/18 00:00 [pmc-release] AID - nu14030424 [pii] AID - nutrients-14-00424 [pii] AID - 10.3390/nu14030424 [doi] PST - epublish SO - Nutrients. 2022 Jan 18;14(3):424. doi: 10.3390/nu14030424.