Lactobacillus reuteri (Limosilactobacillus reuteri) TISTR 2736 Supplementation Attenuates Vascular Injury and Oxidative Stress in Rats Fed a High‐Cholesterol Diet

Hyperlipidemia and oxidative stress are significantly related to atherosclerotic cardiovascular disease. Probiotic supplements have been demonstrated to reduce hyperlipidemia and might minimize atherosclerotic risk. This study aimed to evaluate the therapeutic ability of Lactobacillus reuteri TISTR 2736 (LR) on vascular damage in high-cholesterol diet (HCD)-induced hyperlipidemic rats and elucidate their possible mechanisms. Male Sprague-Dawley rats received a standard diet or HCD, and LR (2 × 10⁸ CFU/rat/day) was orally administered to HCD-fed rats for 8 weeks. Compared to the HCD-fed group, LR administration reduced serum levels of TC, TG, LDL, and endothelin-1 but elevated levels of aortic nitric oxide and serum HDL. Additionally, LR reversed the HCD-induced aortic histological changes. The protein levels of adhesion molecules (VCAM-1 and ICAM-1), lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), NADPH oxidase subunits p47^phox, eNOS monomer/dimer ratio, oxidative stress markers (4-hydroxynonenal and 3-nitrotyrosine), and pro-inflammatory cytokines (TNF-α and IL-6) were decreased, while those of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), and the activity of superoxide dismutase were increased in the aortas of LR-treated rats. These findings suggest that LR supplementation ameliorates HCD-induced vascular dysfunction and inflammation, possibly by lowering hyperlipidemia, suppressing ROS production, and increasing antioxidant enzyme activities.