Non-alcoholic fatty liver disease (NAFLD) has become the main cause of end-stage liver disease. Probiotics have the potential effect of alleviating NAFLD. The aim of this study was to explore functional probiotics and their underlying mechanisms. The bile salt hydrolase (BSH) activity in thirty-four strains was determined in vitro. Then, C57BL/6 mice were used to explore the effects of probiotics on NAFLD. Body weight and food intake were measured, and serum lipid concentrations, oxidative stress and proinflammatory cytokines levels were determined using commercial kits. The expressions of intestinal bile acid pathway genes were evaluated via real-time PCR. The results showed that Lactobacillus casei YRL577 and L. paracasei X11 had higher BSH activity. L. casei YRL577 significantly reduced liver weight and liver index and could regulate the levels of lipid metabolism, oxidative stress and proinflammatory cytokines as compared with L. paracasei X11. Furthermore, the results indicated that L. casei YRL577 up-regulated the mRNA levels of farnesoid X receptor and fibroblast growth factor 15, whereas down-regulated the mRNA level of apical Na-dependent bile acid transporter. These findings suggested that L. casei YRL577 modified genes in the intestinal bile acid pathway which might contribute to the alleviation of NAFLD.

To effectively mitigate antimicrobial resistance in the agricultural ecosystem, there is an increasing pressure to reduce and eliminate the use of in-feed antibiotics for growth promotion and disease prevention in food animals. However, limiting antibiotic use could compromise animal production efficiency and health. Thus, there is an urgent need to develop effective alternatives to antibiotic growth promoters (AGPs). Increasing evidence has shown that the growth-promoting effect of AGPs was highly correlated with the reduced activity of bile salt hydrolase (BSH), an intestinal bacterial enzyme that has a negative impact on host fat digestion and energy harvest; consistent with this finding, the population of Lactobacillus species, the major intestinal BSH-producer, was significantly reduced in response to AGP use. Thus, BSH is a key mechanistic microbiome target for developing novel alternatives to AGPs. Despite recent significant progress in the characterization of diverse BSH enzymes, research on BSH is still in its infancy. This review is focused on the function of BSH and its significant impacts on host physiology in human beings, laboratory animals and food animals. The gaps in BSH-based translational microbiome research for enhanced animal health are also identified and discussed.

CVD affect a large proportion of the world’s population, with dyslipidaemia as the major risk factor. The regular consumption of both probiotic bacteria and yeast has been associated with improvement in the serum lipid profile. Thus, the present review aims to describe and discuss the potential mechanisms responsible for the hypocholesterolaemic effect of regular consumption of probiotic bacteria and yeast. Regarding the hypocholesterolaemic effect of probiotic bacteria, the potential mechanisms responsible include: deconjugation of bile salts; modulation of lipid metabolism; and decreased absorption of intestinal cholesterol through co-precipitation of intestinal cholesterol with the deconjugated bile salts, incorporation and assimilation of cholesterol in the cell membrane of the probiotics, intestinal conversion of cholesterol in coprostanol, and inhibition of the expression of the intestinal cholesterol transporter Niemann–Pick C1 like 1 (NPC1L1) in the enterocytes. The potential mechanisms responsible for the hypocholesterolaemic effect of probiotic yeasts include: deconjugation of bile salts; co-precipitation of intestinal cholesterol with the deconjugated bile salts; incorporation and assimilation of cholesterol in the cell membrane; and inhibition of hepatic cholesterol synthesis. The regular consumption of probiotic bacteria and yeast, as a non-pharmaceutical approach to help manage cardiovascular risk, holds promise, according to the beneficial hypocholesterolaemic effects described herein. However, the hypocholesterolaemic effects vary according to the strains used, the physiological state of the host, and the type of diet to which the probiotics are added. Further studies are necessary to fill the gaps with regard to the knowledge related to this topic.

CVD accounted for 27 % of all deaths in the UK in 2014, and was responsible for 1·7 million hospital admissions in 2013/2014. This condition becomes increasingly prevalent with age, affecting 34·1 and 29·8 % of males and females over 75 years of age respectively in 2011. The dysregulation of cholesterol metabolism with age, often observed as a rise in LDL-cholesterol, has been associated with the pathogenesis of CVD. To compound this problem, it is estimated by 2050, 22 % of the world's population will be over 60 years of age, in culmination with a growing resistance and intolerance to pre-existing cholesterol regulating drugs such as statins. Therefore, it is apparent research into additional therapies for hypercholesterolaemia and CVD prevention is a growing necessity. However, it is also imperative to recognise this complex biological system cannot be studied using a reductionist approach; rather its biological uniqueness necessitates a more integrated methodology, such as that offered by systems biology. In this review, we firstly discuss cholesterol metabolism and how it is affected by diet and the ageing process. Next, we describe therapeutic strategies for hypercholesterolaemia, and finally how the systems biology paradigm can be utilised to investigate how ageing interacts with complex systems such as cholesterol metabolism. We conclude by emphasising the need for nutritionists to work in parallel with the systems biology community, to develop novel approaches to studying cholesterol metabolism and its interaction with ageing.

Several studies have reported limited or no reduction in serum cholesterol in response to probiotic formulations. Recently, probiotics have shown promise in treating metabolic disease due to improved strain selection and delivery technologies. The aim of the present study was to evaluate the cholesterol-lowering efficacy of a yoghurt formulation containing microencapsulated bile salt hydrolase (BSH)-active Lactobacillus reuteri NCIMB 30242, taken twice per d over 6 weeks, in hypercholesterolaemic adults. A total of 114 subjects completed this double-blind, placebo-controlled, randomised, parallel-arm, multi-centre study. This interventional study included a 2-week washout, 2-week run-in and 6-week treatment period. Subjects were randomised to consume either yoghurts containing microencapsulated L. reuteri NCIMB 30242 or placebo yoghurts. Over the intervention period, subjects consuming yoghurts containing microencapsulated L. reuteri NCIMB 30242 attained significant reductions in LDL-cholesterol (LDL-C) of 8·92 % (P = 0·016), total cholesterol (TC) of 4·81 % (P = 0·031) and non-HDL-cholesterol (HDL-C) of 6·01 % (P = 0·029) over placebo, and a significant absolute change in apoB-100 of − 0·19 mmol/l (P = 0·049). Serum concentrations of TAG and HDL-C were unchanged over the course of the study. Present results show that consumption of microencapsulated BSH-active L. reuteri NCIMB 30242 yoghurt is efficacious and safe for lowering LDL-C, TC, apoB-100 and non-HDL-C in hypercholesterolaemic subjects. The efficacy of microencapsulated BSH-active L. reuteri NCIMB 30242 yoghurts appears to be superior to traditional probiotic therapy and akin to that of other cholesterol-lowering ingredients.

The purpose of the present study was to evaluate the anti-hypercholesterolaemic effects of two putative probiotic bile salt hydrolase (Bsh)-producing Lactobacillusplantarum strains, i.e. Lp91 and Lp21, in rats. L. plantarum Lp91 exhibited excellent tolerance to low pH and high bile salt concentrations as well as showed potential Bsh activity, cholesterol assimilation and cholesterol co-precipitation ability along with L. plantarum Lp21 and NCDO82 strains. Furthermore, the potential effect of L. plantarum Lp91 on plasma cholesterol level was evaluated in Sprague–Dawley rats. Five treatment groups of rats (n 6) were fed experimental diets: normal diet, hypercholesterolaemic diet (HD), HD plus L. plantarum Lp91 (HD91) at ≥ 1·0 × 108 colony-forming units (cfu)/g, HD plus microencapsulated L. plantarum Lp91 (HDCap91) at ≥ 1·0 × 108 cfu/g and HD plus L. plantarum Lp21 (HD21) at ≥ 1·0 × 108 cfu/g for 3 weeks. Feed intake and feed efficiency differed significantly among the five groups. After 21 d of dietary treatment, comparative analysis revealed 23·26, 15·71 and 15·01 % reduction in total cholesterol, 21·09, 18·77 and 18·17 % reduction in TAG, 38·13, 23·22 and 21·42 % reduction in LDL-cholesterol, and the corresponding HDL-cholesterol values increased at the rate of 18·94, 10·30 and 7·78 % in treated groups HD91, HDCap91 and HD21, respectively. Faecal excretion of cholic acid and faecal lactobacilli counts were significantly higher in the probiotic treatment groups than in the control groups. In conclusion, these results suggest that the indigenous L. plantarum Lp91 strain has the potential to be explored as a probiotic in the management of hypercholesterolaemia.