Theabrownin as
a Potential Prebiotic Compound Regulates
Lipid Metabolism via the Gut Microbiota, Microbiota-Derived Metabolites,
and Hepatic FoxO/PPAR Signaling Pathways
The
dysregulation of lipid metabolism poses a significant health
threat, necessitating immediate dietary intervention. Our previous
research unveiled the prebiotic-like properties of theabrownin. This
study aimed to further investigate the theabrownin–gut microbiota
interactions and their downstream effects on lipid metabolism using
integrated physiological, genomic, metabolomic, and transcriptomic
approaches. The results demonstrated that theabrownin significantly
ameliorated dyslipidemia, hepatic steatosis, and systemic inflammation
induced by a high-fat/high-cholesterol diet (HFD). Moreover, theabrownin
significantly improved HFD-induced gut microbiota dysbiosis and induced
significant alterations in microbiota-derived metabolites. Additionally,
the detailed interplay between theabrownin and gut microbiota was
revealed. Analysis of hepatic transcriptome indicated that FoxO and
PPAR signaling pathways played pivotal roles in response to theabrownin–gut
microbiota interactions, primarily through upregulating hepatic Foxo1, Prkaa1, Pck1, Cdkn1a, Bcl6, Klf2, Ppara, and Pparg, while downregulating Ccnb1, Ccnb2, Fabp3, and Plin1. These findings underscored the critical role of gut–liver
axis in theabrownin-mediated improvements in lipid metabolism disorders
and supported the potential of theabrownin as an effective prebiotic
compound for targeted regulation of metabolic diseases.