Tormentil Rhizome Ethanolic Extract and Its Gut Microbiota-Derived Metabolites: Modulation of Tight Junction Integrity and Anti-Inflammatory Potential in Caco-2 Cells.

Disruption of intestinal barrier integrity contributes to inflammation, infection, and chronic disease. Tormentil rhizome ethanolic extract (TR-EtOH), traditionally used in functional alcoholic beverages, is rich in polyphenols that undergo extensive gut microbiota metabolism. This study evaluated the phytochemical composition, total phenolic content, antioxidant activity, and barrier-protective effects of TR-EtOH and its gut-derived metabolites (TREMs). Microbiota metabolism markedly reduced phenolic content and antioxidant activity, consistent with the degradation of polymeric tannins. Biological activity was investigated in a Clostridioides difficile toxin-induced Caco-2 model using TEER, qPCR, Western blot, and cytokine secretion assays. TR-EtOH preserved epithelial integrity and reduced inflammatory responses, whereas TREMs showed donor-dependent effects on barrier stabilization and cytokine modulation. These findings indicate that native tormentil polyphenols and microbiota-derived metabolites may protect the intestinal barrier through complementary mechanisms, supporting their potential use in functional food and beverage development.