Key result
Non-absorbable oral antibiotics increase aortic root atherosclerosis independently of diet in preclinical models.
Why the study?
Gut bacteria metabolism is linked to CVD and influenced by diet and antibiotics, but whether oral antibiotic treatment negatively affects atherosclerosis independently of diet and through which underlying pathways remained to be clarified.
Does oral non-absorbable antibiotic treatment increase histological atherosclerosis independently of diet in Apolipoprotein E-deficient mice?
Does oral non-absorbable antibiotic treatment increase histological atherosclerosis independently of diet in Apolipoprotein E-deficient mice?
Preclinical investigation demonstrating that oral non-absorbable antibiotics promote atherosclerosis independently of diet in ApoE-deficient mice, mediated by alterations in gut bacterial metabolism and serum metabolites.
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Should not alter antibiotic prescribing; leaves open microbiome-targeted vascular prevention in humans.
Purpose: Gut bacteria metabolism has been linked to cardiovascular disease (CVD). The intestinal flora can be influenced by many environmental factors such as diet and antibiotics. Purpose of the study was to assess if oral antibiotics treatment (ABX) could negatively affect atherosclerosis independently of diet and unveil the underlying pathways using a state-of-the-art bioinformatics approach. Methods: Apolipoprotein E-deficient mice (C57BL/6J background; n=26) were divided into 4 groups: normal diet untreated (ND-UT), normal diet with oral largely non-absorbable ABX (ND-ABX), Western diet without antibiotics (WD-UT) and Western diet with ABX (WD-ABX). After 16 weeks, degree of atherosclerosis was evaluated histologically at the aortic root level. We used 16S metagenomics of gut bacteria and untargeted serum metabolomics to study the potential mechanisms. Data were analysed using different bioinformatics tool such as KEGG pathway analysis of intestinal bacteria by PICRUSt/HUMAnN and clustering of serum metabolites by weighted correlation network analysis (WGCNA). In a next step, human umbilical vein endothelial cells (HUVECs) were treated with gut-derived metabolites, which were identified in the previous experiment, and analysed for proliferation by BrDU assay and metabolic function by Seahorse Flux Analyser.
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Kappel et al. (2017) studied Atherosclerosis (n=26). Oral largely non-absorbable antibiotics (ABX) on normal or Western diet, and gut-derived metabolites in HUVECs vs. Untreated normal diet (ND-UT) and untreated Western diet (WD-UT) was evaluated on Histological degree of atherosclerosis at the aortic root level. Oral largely non-absorbable antibiotics increased atherosclerosis independently of diet in Apolipoprotein E-deficient mice (n=26) over 16 weeks.
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