Suppression of Gut Dysbiosis Reverses Western Diet-Induced Vascular Dysfunction

Objective. Vascular dysfunction represents a critical pre-clinical step in the development of cardiovascular disease. We examined the role of the gut microbiota in the development of obesity-related vascular dysfunction. Approach and Results. Male C57BL/6J mice were fed either a standard diet (SD) (n=12) or western diet (WD) (n=24) for 5m, after which time, WD mice were randomized to receive either un-supplemented drinking water or water containing a broad-spectrum antibiotic cocktail (WD+Abx) (n=12/group) for 2m. Seven months of WD caused gut dysbiosis, increased arterial stiffness (SD: 412.0{plus minus}6.0 vs WD: 458.3{plus minus}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{plus minus}.23 vs WD: 11{plus minus}0.86 µg/mL, p<0.05) and interleukin-6 (IL-6) (SD: 3.27{plus minus}0.25 vs WD: 7.09{plus minus}1.07 pg/mL, ...