Gut Microbial Catabolism of Prebiotic Theabrownin Yields Bioactive Metabolites for Gut Health and Lipid Homeostasis

Although theabrownin (TB), a polymeric phenolic pigment from dark tea, has shown promise in metabolic regulation for health, its gastrointestinal transformation and underlying mechanisms remain poorly understood. Here, we present the first systematic investigation into the gastrointestinal catabolism and microbiota-targeted bioactivity of TB using an integrated <i>in vitro</i> digestion and colonic fermentation model. TB exhibited limited bioaccessibility in the upper gastrointestinal tract but underwent extensive microbial biotransformation in the colon, releasing phenolic metabolites (e.g., flavonoids, phenylpropanoids) that enhanced antioxidant capacity and increased short-chain fatty acid production, particularly acetate and propionate. Fermentation of TB significantly modulated gut microbiota by enriching beneficial genera and suppressing pathogenic taxa. Notably, TB-derived microbial metabolites inhibited cholesterol uptake in Caco-2 cells via NPC1L1 downregulation and ABCA1 upregulation. This study first reveals TB's <i>in vitro</i> digestion dynamics, underscoring its potential as a microbiota-targeted prebiotic for lipid regulation and metabolic health in functional foods.