Multi-Omics Reveals Inhibitory Effect of Baicalein on Non-Alcoholic Fatty Liver Disease in Mice

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, whose etiology is poorly understood. Accumulating evidence indicates that gut microbiota plays an important role in the occurrence and progression of various human diseases, including NAFLD. In this study, NAFLD mouse models were established by feeding a high-fat diet (HFD). Baicalein, a natural flavonoid with multiple biological activities, was administered by gavage, and its protective effect on NAFLD was analyzed by histopathological and blood factor analysis. Gut microbiota analysis demonstrated that baicalein could remodel the overall structure of the gut microbiota from NAFLD model mice, especially Anaerotruncus, Lachnoclostridium, and Mucispirillum. Transcriptomic analysis showed baicalein restored the expressions of numerous genes that were upregulated in hepatocytes of NAFLD mice, such as Apoa4, Pla2g12a, Elovl7, Slc27a4, Hilpda, Fabp4, Vldlr, Gpld1, and Apom. Metabolomics analysis proved that baicalein mainly regulated the processes associated with lipid metabolism, such as alpha-Linolenic acid, 2-Oxocarboxylic acid, Pantothenate and CoA biosynthesis, and bile secretion. Multi-omics analysis revealed that numerous genes regulated by baicalein were significantly correlated with pathways related to lipid metabolism and biosynthesis and secrection of bile acid, and baicalein might affect lipid metabolism in liver via regulating the ecological structure of gut microbiota in NAFLD mice. Our results elucidated the correlated network among diet, gut microbiota, metabolomic, and transcriptional profiling in the liver. This knowledge may help explore novel therapeutic approaches against NAFLD.

Dendrobium officinale alleviates high-fat diet-induced nonalcoholic steatohepatitis by modulating gut microbiota

“…At the genus and species level, changes in microbiota richness and diversity during NASH were primarily associated with Romboutsia ( Zeng et al., 2019 ), Turicibacter , Lachnoclostridium ( Li et al., 2022 ), Blautia ( Vallianou et al., 2021 ), Ruminococcus_torques_group , Sutterella , Escherichia-Shigella, Prevotella , Alistipe , and Lactobacillus_acidophilus . Escherichia-Shigella produces ethanol that can damage the intestinal mucosa and promote liver inflammation ( Zhu et al., 2013 ), Sutterella has pro-inflammatory effects on the gastrointestinal tract ( Hiippala et al., 2016 ), and Escherichia-Shigella and Sutterella , both belonging to the Proteobacteria phylum, induce LPS biosynthesis ( Song et al., 2017 ; Xu et al., 2018 ).…”

Fagopyrum dibotrys extract alleviates hepatic steatosis and insulin resistance, and alters autophagy and gut microbiota diversity in mouse models of high-fat diet-induced non-alcoholic fatty liver disease

“…The gut microbiota plays an important role in the progression of NAFLD, and gut microbiota dysbiosis is a key factor in NAFLD pathogenesis (30)(31)(32). Based on 16S rRNA gene sequencing analysis, we investigated whether 10.3389/fnut.2022.993501 the gut microbiota was influenced by FDE treatment.…”

Green Pea (Pisum sativum L.) Hull Polyphenol Extract Alleviates NAFLD through VB6/TLR4/NF-κB and PPAR Pathways

“…The combination of multiomics technology can more effectively analyze the potential mechanism of NAFLD. Combined metabolomics and transcriptomics found that Hassk fruit polyphenol extract relieves NAFLD through the TLR4-NKKB pathway and that the positive effect of baicalein on NAFLD may be related to the regulation of lipid metabolism by gut flora …”

“…Combined metabolomics and transcriptomics found that Hassk fruit polyphenol extract relieves NAFLD through the TLR4-NKKB pathway 12 and that the positive effect of baicalein on NAFLD may be related to the regulation of lipid metabolism by gut flora. 13 Due to its complex pathogenesis, there are so far no drugs approved to treat NAFLD, although some drugs, such as semaglutide, are undergoing clinical trials. 14 Natural active food ingredients (e.g., polyphenols, saponins, polysaccharides) have been widely studied for their physiological activities on NAFLD.…”