Lactobacillus fermentum CECT5716 prevents renal damage in the NZBWF1 mouse model of systemic lupus erythematosus

Abstract

The aim of this work was to evaluate whether the immune-modulatory bacterium Lactobacillus fermentum CECT5716 (LC40) protects the kidneys in a female mouse model of lupus with hypertension. Twenty-week-old female NZBWF1 (lupus) and NZW/LacJ (control) mice were treated with vehicle or LC40 (5 × 10⁸ colony-forming units day⁻¹) for 13 weeks. LC40 treatment reduced the increased plasma anti-dsDNA, endotoxemia, and high blood pressure in NZBWF1 mice. In parallel, LC40 also prevented alterations in kidney function parameters, measured by reduced creatinine and urea in urine excretion, and kidney injury, evaluated by albumin excretion in lupus mice. The main histological features found in the kidneys of lupus mice, such as glomerular, tubulointerstitial or vascular lesions present in the renal parenchyma, accompanied by immune-complex deposition and inflammatory infiltrates were also reduced by LC40. In addition, LC40 inhibited the increased levels of pro-inflammatory cytokines, NADPH oxidase activity and infiltration of Th17 and Th1 cells in the kidneys of NZBWF1 mice. Interestingly, no significant changes were observed in control mice treated with LC40. In conclusion, these results indicate that the consumption of LC40 can prevent the impairment of kidney function and damage, in part due to its capacity to reduce anti-dsDNA production and circulating levels of lipopolysaccharides, with the subsequent reduction of immune complex deposition, inflammation and oxidative stress. These results open new possibilities for the prevention of renal complications associated with hypertensive systemic lupus erythematosus by the chronic administration of the probiotic LC40.