Cranberry extract-supplemented microbiota effluents enhance intestinal barrier integrity via mucin production and antimicrobial activity in murine organoids

Cranberry extract (CE), rich in proanthocyanidins (PACs) and oligosaccharides, interacts with gut microbiota to produce bioactive metabolites that may enhance intestinal barrier function. However, its direct and microbiota-mediated effects on intestinal epithelial cells remain unclear. This study examined CE gut microbial metabolism on host epithelial responses using an ex vivo fermentation system and an in vivo intestinal organoid model. CE (86.8 mg PACs/day) was administered in the TWIN-M-SHIME system with fecal samples from healthy donors over two weeks. Fermentation effluents were incubated with murine intestinal organoids, and gene expression analysis was performed. Organoid incubation with CE-supplemented effluents upregulated Muc2, Atoh1, and Klf4, suggesting enhanced goblet cell differentiation and mucin production. Defa20 expression increased, indicating stronger antimicrobial defense. GPR109a and GPR43 upregulation correlated with butyrate, linking microbial metabolism to epithelial reinforcement. These findings suggest that CE could promote intestinal barrier function through both direct and microbiota-dependent epithelial effects. Cranberry supplementation may serve as functional dietary interventions to support gut health.