Untitled IteElucidating the Gut Microbiota-Driven Crosstalk: Mechanistic Interplay of Lobetyolin in Coordinating Cholesterol Homeostasis and Anti-Inflammatory Pathways in Hyperlipidemic Mice Modelsm

the objective of this study is to investigate the molecular processes by which lobetyolin modifies gut microbiota to improve intestinal inflammation and lipid metabolism abnormalities in hyperlipidemic mice. This study provides a theoretical basis for the development of natural product therapies that focus on multi-target regulation by elucidating the critical role of lobetyolin in controlling the ecological network of gut microbiota and its related regulatory pathways in the host's metabolic immune network. The results indicate that LBT can reduce the expression of SREBP2 and HMGCR, thereby decreasing the generation of endogenous cholesterol. Lobetyolin enhances the expression of ABCA1, ABCG5, ABCG8, and LDLR, promoting reverse cholesterol transport and facilitating the clearance of cholesterol from peripheral tissues. Additionally, Lobetyolin exerts anti-inflammatory effects via the TLR4/NF - κ B signaling pathway, regulates Th1 and Th2 immune responses, and enhances the immune potential of the colonic mucosa. Based on 16S rRNA sequencing data, LBT therapy increased the abundance of beneficial bacteria, including Akkermansia, Dubosiella, Parasottella, Lactobacillus, Bacteroides, and Paramuribaculum. The abundance of these beneficial bacteria was positively correlated with HDL-C, SIgA, IL-4, and IL-10, and negatively correlated with IL-6, INF-γ, TNF-α, INF-γ/IL-4, and INF-γ/IL-10. In summary, our study not only provides empirical evidence for LBT's regulation of metabolic liver disease by Lobetyolin but also emphasizes its importance in the ecological structure of the gut microbiota and its interaction with the host metabolic immune network in diseases.