Ganoderma lucidum spore oil ameliorates high-fat-diet-induced hepatic lipid metabolism disorder by modulation of the gut microbiota.

BACKGROUND: Obesity is a major global public health challenge. A high-fat diet (HFD) is a key contributing factor, closely associated with gut microbiota dysbiosis. Although immunomodulatory effects of Ganoderma lucidum spore oil (GLSO) have been reported, its role in lipid metabolism disorders and its interaction with gut microbiota remain incompletely understood. RESULTS: In this study, an HFD-induced obese mouse model was established and treated with GLSO (800 mg kg-1 day-1) for 82 days. Integrated analyses - including 16S rRNA sequencing, metabolomics, fecal fermentation of GLSO (FGLSO), and HepG2 cell experiments - were performed to evaluate metabolic effects and potential microbiota-related mechanisms. Ganoderma lucidum spore oil significantly reduced body weight gain, fasting blood glucose, serum lipid levels - including total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) - and inflammatory markers, specifically tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6). It also improved gut microbiota composition by increasing microbial diversity and enriching beneficial taxa such as Bacillus and unclassified_Muribaculaceae. These changes were accompanied by increased levels of short-chain fatty acids (SCFAs), particularly acetate and propionate, as well as alterations in bile acid metabolism. Further analysis suggested that metabolites may be associated with the regulation of hepatic lipid metabolism, potentially involving the peroxisome proliferator-activated receptor alpha (PPARα) signaling pathway. Fecal fermentation of GLSO exhibited stronger lipid-lowering effects than native GLSO in vitro, indicating that gut microbiota-mediated biotransformation may enhance the bioactivity of GLSO. CONCLUSION: Collectively, these findings suggest that GLSO alleviates HFD-induced metabolic disorders and highlight a potential role of gut microbiota in modulating its metabolic effects and enhancing its bioactivity. © 2026 Society of Chemical Industry.