Effect of Lactobacillus delbrueckii on cholesterol metabolism in germ-free mice and on atherogenesis in apolipoprotein E knock-out mice

Abstract

Elevated blood cholesterol is an important risk factor associated with atherosclerosis and coronary heart disease. Several studies have reported a decrease in serum cholesterol during the consumption of large doses of fermented dairy products or lactobacillus strains. The proposed mechanism for this effect is the removal or assimilation of intestinal cholesterol by the bacteria, reducing cholesterol absorption. Although this effect was demonstrated in vitro, its relevance in vivo is still controversial. Furthermore, few studies have investigated the role of lactobacilli in atherogenesis. The aim of the present study was to determine the effect of Lactobacillus delbrueckii on cholesterol metabolism in germ-free mice and the possible hypocholesterolemic and antiatherogenic action of these bacteria using atherosclerosis-prone apolipoprotein E (apo E) knock-out (KO) mice. For this purpose, Swiss/NIH germ-free mice were monoassociated with L. delbrueckii and fed a hypercholesterolemic diet for four weeks. In addition, apo E KO mice were fed a normal chow diet and treated with L. delbrueckii for 6 weeks. There was a reduction in cholesterol excretion in germfree mice, which was not associated with changes in blood or liver cholesterol concentration. In apo E KO mice, no effect of L. delbrueckii was detected in blood, liver or fecal cholesterol. The atherosclerotic lesion in the aorta was also similar in mice receiving or not these bacteria. In conclusion, these results suggest that, although L. delbrueckii treatment was able to reduce cholesterol excretion in germ-free mice, no hypocholesterolemic or antiatherogenic effect was observed in apo E KO mice. Correspondence

Absence of Microbiota (Germ-Free Conditions) Accelerates the Atherosclerosis in ApoE-Deficient Mice Fed Standard Low Cholesterol Diet

“…Administration of probiotic bacteria led to reduction of the cardiovascular disease risk factors and it was suggested as a protective agent in the primary prevention of atherosclerosis in smokers 30) . On the other hand, in conventional knockout ApoE / mice on a hypercholesteric diet, administration of L. delbrüeckii had only a low antiatherogenic effect 31) . A specific strain of L. plantarum (DSM 9843) was used in probiotic therapy of incipient atherosclerosis in humans, and increased bacterial diversity in the gut and changes in the concentration of some short chain fatty acids produced by bacteria as a consequence of lactobacilli administration were described 32) .…”

Lactobacillus acidophilus ATCC 4356 Prevents Atherosclerosis via Inhibition of Intestinal Cholesterol Absorption in Apolipoprotein E-Knockout Mice

“…Only a few studies have investigated the effect of lactobacilli intervention on the development of atherosclerosis in animal models. Portugal et al (15) investigated whether Lactobacillus delbrueckii reduces atherosclerosis by colonizing conventionally raised ApoE-knockout (ApoE Ϫ/Ϫ ) mice, but they observed no significant effects on atherosclerotic lesion size, which may be explained by the fact that the bacterium did not alter the blood cholesterol levels.…”

Effects of gut microbiota on obesity and atherosclerosis via modulation of inflammation and lipid metabolism

“…Portugal et al. investigated whether Lactobacillus delbruecki reduces atherosclerosis by colonizing conventionally raised ApoE−/− mice, but observed no significant effects on atherosclerotic lesion size [87], which may be explained by the fact that the bacterium did not alter blood cholesterol levels. By contrast, administration of prebiotics to ApoE−/− mice for 16 weeks, which had more dramatic effects on the gut microbial composition, reduced atherosclerotic lesion size by 35% [88].…”