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Gut microbiota dysbiosis augments atherosclerosis in LDLR-/- mice
- Source :
- Atherosclerosis. 263
- Publication Year :
- 2017
-
Abstract
- Aim: In recent years the gut microbiome has been recognized as an important participant in the etiology of obesity and -associated comorbidities. Moreover, recent studies have implicated an involvement of the gut microbiota in both cardiovascular health and disease. Although the gut microbiome has been suggested as a contributor to atherosclerosis, firm evidence to support a causal role for the gut microbiota in atherosclerosis is limited. Methods: To investigate the effect of the gut microbiota in atherosclerosis, we performed fecal microbiota transplantation to transplant the gut microbiota of caspase1-/- mice, an established model for dysbiosis, into LDLR-/- mice (LDLR-/-[casp1-/-]). Fecal microbiota transplantation of the gut microbiota of LDLR-/- mice into LDLR-/- mice (LDLR-/-[LDLR-/-]) served as control. Mice were fed a chow or high-fat cholesterol diet (HFC, 0,21% cholesterol) for 13 weeks and fecal samples were collected to determine microbiota composition by 16S rRNA sequencing. Plaque size was analyzed in the aortic root and immune cell subsets were analyzed by flow cytometry. Results: 16S rRNA sequencing of fecal samples confirmed the induction of dysbiosis in LDLR-/-[casp1-/-] compared to LDLR-/-[LDLR-/-] mice. Body weight, plasma triglyceride and cholesterol levels were significantly increased by HFC-feeding in LDLR-/-[casp1-/-] and LDLR-/-[LDLR-/-] mice. However, dysbiosis did not affect these parameters. In contrast, plaque size was significantly increased in HFC-fed LDLR-/-[casp1-/-] compared to HFC-fed (LDLR-/-[LDLR-/-] mice. Furthermore, dysbiosis in LDLR-/- mice was associated with a moderate increase in circulatory levels of Ly6C-high monocytes. Conclusions: Our data shows that gut microbiota dysbiosis augments atherosclerosis, possibly by exacerbating low-grade systemic inflammation.
- Subjects :
- 0301 basic medicine
030204 cardiovascular system & hematology
Gut flora
Systemic inflammation
digestive system
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Immune system
Medicine
cardiovascular diseases
Feces
biology
business.industry
Cholesterol
food and beverages
nutritional and metabolic diseases
biology.organism_classification
medicine.disease
Obesity
030104 developmental biology
chemistry
LDL receptor
Immunology
lipids (amino acids, peptides, and proteins)
medicine.symptom
Cardiology and Cardiovascular Medicine
business
Dysbiosis
Subjects
Details
- Language :
- English
- ISSN :
- 00219150
- Volume :
- 263
- Database :
- OpenAIRE
- Journal :
- Atherosclerosis
- Accession number :
- edsair.doi.dedup.....774770a71db1b325e2a14359b6695964