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Abstract
Hypercholesterolaemia is a major risk factor for cardiovascular disease and it has been found that some probiotic bacteria possess cholesterol-lowering capabilities. In this study, the ability of the Lab4 probiotic consortium to hydrolyse bile salts, assimilate cholesterol and regulate cholesterol transport by polarised Caco-2 enterocytes was demonstrated. Furthermore, in wild-type C57BL/6J mice fed a high fat diet, 2-weeks supplementation with Lab4 probiotic consortium plus Lactobacillusplantarum CUL66 resulted in significant reductions in plasma total cholesterol levels and suppression of diet-induced weight gain. No changes in plasma levels of very low-density lipoprotein/low-density lipoprotein, high-density lipoprotein, triglycerides, cytokines or bile acids were observed. Increased amounts of total and unconjugated bile acids in the faeces of the probiotic-fed mice, together with modulation of hepatic small heterodimer partner and cholesterol-7α-hydroxylase mRNA expression, implicates bile salt hydrolase activity as a potential mechanism of action. In summary, this study demonstrates the cholesterol-lowering efficacy of short-term feeding of the Lab4 probiotic consortium plus L. plantarum CUL66 in wild-type mice and supports further assessment in human trials.
Highlights
Cardiovascular disease (CVD) is the cause of death in one in three people in the United Kingdom[1] and is the leading cause of global mortality[2]
There are multiple mechanisms by which these effects are thought to occur including the assimilation of cholesterol[22] and/or the deconjugation of bile salts by bile salt hydrolase (BSH) positive probiotic bacteria that put increased demand on de novo bile synthesis to replace that which is lost in faeces[23, 24]
High circulating levels of TC and obesity are associated with increased risk of CVD and reductions in cholesterol levels and body weight can have a beneficial impact on this disease[2]
Summary
Cardiovascular disease (CVD) is the cause of death in one in three people in the United Kingdom[1] and is the leading cause of global mortality[2]. Hypercholesterolaemia is a major risk factor for the disease and statins are widely used to normalise elevated circulating cholesterol levels and can reduce CVD-related events by approximately 25%3–7 and are often associated with adverse side effects[8]. The high mortality rates associated with CVD suggest these measures are not sufficiently effective and further options are required[10,11,12]. Assessment of the cholesterol lowering capabilities of Lab[4] was made in vitro prior to its inclusion, in combination with L. plantarum CUL66, in a short-term feeding study with C57BL/6J mice on a high fat diet
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