Lactobacillus fermentum CECT5716: a novel alternative for the prevention of vascular disorders in a mouse model of systemic lupus erythematosus

Abstract

The aim of the present study was to examine whether the immune-modulatory bacteria Lactobacillusfermentum CECT5716 (LC40) ameliorates disease activity and cardiovascular complications in a female mouse modelof lupus. Eighteen-week-old NZBWF1 [systemic lupus erythematosus (SLE)] and NZW/LacJ (control) mice weretreated with vehicle or LC40 (5 3 108 colony-forming units/d) for 15 wk. LC40 treatment reduced lupus diseaseactivity, blood pressure, cardiac and renal hypertrophy, and splenomegaly in SLE mice. LC40 reduced the elevated T,B, regulatory T cells (Treg), and T helper (Th)-1 cells in mesenteric lymph nodes of lupus mice. LC40 lowered thehigher plasma concentration of proinflammatory cytokines observed in lupus mice. Aortas from SLE mice showedreduced endothelium-dependent vasodilator responses to acetylcholine. Endothelial dysfunction found in SLE isrelated to an increase of both NADPH oxidase-driven superoxide production and eNOS phosphorylation at theinhibitory Thr495. These activities returned to normal values after a treatment with LC40. Probiotic administration toSLE mice reduced plasma LPS levels, which might be related to an improvement of the gut barrier integrity. LC40treatment increases the Bifidobacterium count in gut microbiota of SLE mice. In conclusion, our findings identify thegut microbiota manipulation with LC40 as an alternative approach to the prevention of SLE and its associatedvascular damage.