Bile salt hydrolase-overexpressing Lactobacillus strains can improve hepatic lipid accumulation in vitro in an NAFLD cell model

Abstract

Background Non-alcoholic fatty liver disease (NAFLD) includes a range of liver diseases that occur in the absence of significant alcohol consumption. The probiotic bacterial strains Lactobacillus casei LC2W, which overexpresses the bile salt hydrolase (BSH) gene (referred to as pWQH01), and Lactobacillus plantarum AR113, which exhibits high BSH activity, have been shown to improve hepatic lipid accumulation and may lower cholesterol levels in vivo . These effects may be BSH-dependent, as L. casei LC2W without BSH activity did not exert these beneficial effects. Objective This study aimed to investigate the effects of Lactobacillus with high BSH activity on cholesterol accumulation and lipid metabolism abnormalities in oleic acid (OA)- and cholesterol-induced HepG2 cell models, and to determine the mechanism underlying the effects. Design A HepG2 cell model of OA-induced steatosis and cholesterol-induced cholesterol accumulation was developed. OA- and cholesterol-treated HepG2 cells were incubated with L. plantarum AR113, L. casei LC2W or L. casei pWQH01 for 6 h at 37°C with 5% CO 2 . Subsequently, a series of indicators and gene expressions were analysed. Results Both L. plantarum AR113 and L. casei pWQH01 significantly reduced lipid accumulation, total cholesterol (TC) levels and 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) mRNA expression relative to the control group, whereas L. casei LC2W had no similar effect. Additionally, exposure to L. plantarum AR113 or L. casei pWQH01 significantly reduced the expression of sterol regulatory element-binding protein 1c (SREBP-1c), Acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS) and tumour necrosis factor-α (TNF-α) andsignificantly increased the expression of 5' adenosine monophosphate-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor alpha (PPARα). Conclusion Both L. plantarum AR113 and L. casei pWQH01 appear to improve steatosis in vitro in a BSH-dependent manner.

Probiotics Interact With Lipids Metabolism and Affect Gut Health

“…Several probiotic strains have been extensively studied and their benefits to human health have been widely documented. For example, it has been reported that probiotics, such as Bifidobacterium longum , Lactobacillus acidophilus , L. casei, L. plantarum , exhibit bile salt hydrolases ( 42 , 72 – 74 , 80 , 81 ). For example, L. casei pWQH01, which overexpresses bsh 1 from L. plantarum AR113, appear to improve steatosis in vitro in a BSH-dependent manner ( 81 ).…”

“…For example, it has been reported that probiotics, such as Bifidobacterium longum , Lactobacillus acidophilus , L. casei, L. plantarum , exhibit bile salt hydrolases ( 42 , 72 – 74 , 80 , 81 ). For example, L. casei pWQH01, which overexpresses bsh 1 from L. plantarum AR113, appear to improve steatosis in vitro in a BSH-dependent manner ( 81 ). Lactobacillus gasseri BNR17 can inhibit the secretion of adiponectin and leptin, and reduce adipose tissue, while L. gasseri SBT2055 reduced mesenteric tissue mass, serum leptin levels and adipocyte size in lean Zucker mice ( 82 , 83 ).…”

Bile Salt Hydrolases: At the Crossroads of Microbiota and Human Health

“…Other probiotics, tested either in combination or isolated, also showed beneficial effects on NAFLD improvement [ 45 , 46 ]. Recently, Huang et al demonstrated that Lactobacillus plantarum AR113 and L. casei pWQH0, which both display high BSH activity, decrease hepatic lipid accumulation in NAFLD cell models, which is potentially mediated by the BSH activity [ 47 ]. Besides cholesterol and lipid metabolism, BSH activity may be linked to inflammatory disorders.…”

Probiotic Effector Compounds: Current Knowledge and Future Perspectives

“…However, the mechanism behind the hypocholesterolemic ability of probiotics remains elusive. Yet one of the most reported mechanism has been attributed to the ability of some probiotics to produce bile salt hydrolase (BSH; Jones et al, 2012 ; Wang et al, 2019a ; Huang et al, 2020 ). Many probiotic bacteria, such as L. plantarum WCFS1, L. plantarum TH1, and Bifidobacteria longum SBT2928, produce BSH ( Ishimwe et al, 2015 ), which can hydrolyze conjugated bile salts, such as taurine-conjugated bile salts and glycine-conjugated bile salts, to release primary bile acids ( Li et al, 2020 ).…”