Suppression of gut dysbiosis reverses Western diet-induced vascular dysfunction

Vascular dysfunction represents a critical preclinical step in the development of cardiovascular disease. We examined the role of the gut microbiota in the development of obesity-related vascular dysfunction. Male C57BL/6J mice were fed either a standard diet (SD) ( n = 12) or Western diet (WD) ( n...

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Bibliographic Details
Published in:American journal of physiology: endocrinology and metabolism 2018-05, Vol.314 (5), p.E468-E477
Main Authors: Battson, Micah L, Lee, Dustin M, Jarrell, Dillon K, Hou, Shuofei, Ecton, Kayl E, Weir, Tiffany L, Gentile, Christopher L
Format: Article
Language:English
Subjects:
Abnormalities
Advanced glycosylation end products
Animals
Anti-Bacterial Agents - pharmacology
Anti-Bacterial Agents - therapeutic use
Antibiotics
Aorta
Body weight
Cardiovascular disease
Cardiovascular diseases
Diet
Diet, Western - adverse effects
Dilation
Drinking water
Dysbacteriosis
Dysbiosis - complications
Dysbiosis - drug therapy
Dysbiosis - physiopathology
Gastrointestinal Microbiome - drug effects
Glucose tolerance
Glycosylation
Interleukin 6
Intestinal microflora
Lipopolysaccharides
LPS-binding protein
Male
Mice
Mice, Inbred C57BL
Mice, Obese
Microbiota
NAD(P)H oxidase
NF-κB protein
NG-Nitroarginine methyl ester
Obesity
Obesity - drug therapy
Obesity - etiology
Obesity - microbiology
Obesity - physiopathology
Proteins
Stiffness
Therapeutic applications
Vascular Diseases - complications
Vascular Diseases - etiology
Vascular Diseases - physiopathology
Vascular Diseases - prevention & control
Vascular Stiffness - drug effects
Vein & artery diseases
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Summary:Vascular dysfunction represents a critical preclinical step in the development of cardiovascular disease. We examined the role of the gut microbiota in the development of obesity-related vascular dysfunction. Male C57BL/6J mice were fed either a standard diet (SD) ( n = 12) or Western diet (WD) ( n = 24) for 5 mo, after which time WD mice were randomized to receive either unsupplemented drinking water or water containing a broad-spectrum antibiotic cocktail (WD + Abx) ( n = 12/group) for 2 mo. Seven months of WD caused gut dysbiosis, increased arterial stiffness (SD 412.0 ± 6.0 vs. WD 458.3 ± 9.0 cm/s, P < 0.05) and endothelial dysfunction (28% decrease in max dilation, P < 0.05), and reduced l-NAME-inhibited dilation. Vascular dysfunction was accompanied by significant increases in circulating LPS-binding protein (LBP) (SD 5.26 ± 0.23 vs. WD 11 ± 0.86 µg/ml, P < 0.05) and interleukin-6 (IL-6) (SD 3.27 ± 0.25 vs. WD 7.09 ± 1.07 pg/ml, P < 0.05); aortic expression of phosphorylated nuclear factor-κB (p-NF-κB) ( P < 0.05); and perivascular adipose expression of NADPH oxidase subunit p67phox ( P < 0.05). Impairments in vascular function correlated with reductions in Bifidobacterium spp. Antibiotic treatment successfully abrogated the gut microbiota and reversed WD-induced arterial stiffness and endothelial dysfunction. These improvements were accompanied by significant reductions in LBP, IL-6, p-NF-κB, and advanced glycation end products (AGEs), and were independent from changes in body weight and glucose tolerance. These results indicate that gut dysbiosis contributes to the development of WD-induced vascular dysfunction, and identify the gut microbiota as a novel therapeutic target for obesity-related vascular abnormalities.
ISSN:0193-1849
1522-1555
DOI:10.1152/AJPENDO.00187.2017