Lactiplantibacillus plantarum LPJZ-658 Improves Non-Alcoholic Steatohepatitis by Modulating Bile Acid Metabolism and Gut Microbiota in Mice

Abstract

Non-alcoholic steatohepatitis (NASH) is one of the most prevalent diseases worldwide; it is characterized by hepatic lipid accumulation, inflammation, and progressive fibrosis. Here, a Western diet combined with low-dose weekly carbon tetrachloride was fed to C57BL/6J mice for 12 weeks to build a NASH model to investigate the attenuating effects and possible mechanisms of Lactiplantibacillus plantarum LPJZ-658. Hepatic pathology, lipid profiles, and gene expression were assessed. The metabolomic profiling of the serum was performed. The composition structure of gut microbiota was profiled using 16s rRNA sequencing. The results show that LPJZ-658 treatment significantly attenuated liver injury, steatosis, fibrosis, and inflammation in NASH mice. Metabolic pathway analysis revealed that several pathways, such as purine metabolism, glycerophospholipid metabolism, linoleic acid metabolism, and primary bile acid biosynthesis, were associated with NASH. Notably, we found that treatment with LPJZ-658 regulated the levels of bile acids (BAs) in the serum. Moreover, LPJZ-658 restored NASH-induced gut microbiota dysbiosis. The correlation analysis deduced obvious interactions between BAs and gut microbiota. The current study indicates that LPJZ-658 supplementation protects against NASH progression, which is accompanied by alternating BA metabolic and modulating gut microbiota.

Exploring the Regulatory Effect of LPJZ-658 on Copper Deficiency Combined with Sugar-Induced MASLD in Middle-Aged Mice Based on Multi-Omics Analysis

“…Our practice has confirmed that LPJZ-658 improves lipid metabolism in late-laying laying hens and broiler chickens [39]. It is important to note that we found that LPJZ-658 ameliorated hepatic steatosis, inflammation, and fibrosis in NASH model mice by mediating bile acid metabolism and the gut microbiota [29], which suggests that LPJZ-658 has the potential to improve MASLD. In this study, copper deficiency combined with a high-sugar-diet-induced MASLD mouse model was used to explore the therapeutic mechanism of LPJZ-658 in MASLD-combined lipidomics, metabolomics, and gut microbiota strategies.…”

“…Therefore, metabolomics may provide more insights and clues for the present study on the development and progression of copper deficiency combined with sugar-induced MASLD and the mechanism of action of LPJZ-658. In our previous studies, LPJZ-658 has been found to affect multiple metabolic pathways, especially bile acid biosynthesis [29].…”

“…Lactiplantibacillus plantarum LPJZ-658 is a probiotic strain newly isolated by our group [28]. In our previous study, we used metabolomics and gut microbiota analyses and found that LPJZ-658 mitigated the development of NASH by correcting the dysregulation of bile acid metabolism and modulating the gut microbiota [29]; thus, its potential role in improving MASLD was clarified.…”

Integrated Microbiome and Serum Metabolome Analysis Reveals Molecular Regulatory Mechanisms of the Average Daily Weight Gain of Yorkshire Pigs

“…A robust correlation exists between the gut microbiota and serum metabolites. Using 16S rRNA sequencing and serum metabolomics, Oscillibacter demonstrated a positive correlation with chenodeoxycholic acid, glycocholic acid, and deoxycholic acid [18]. The glucose and lipid metabolic pathways in the host can be modulated using SCFAs originating from microbial sources, and SCFAs have the capacity to exert an influence on immune function and inflammation [19].…”