Evaluation of the prebiotic potential of polyphenol-rich plant extracts in a mouse model of colitis

Graphical Abstract Abstract Objective: Intestinal inflammation is linked to gut dysbiosis and disrupted host–microbe interactions. This study investigated four plant extracts rich in polyphenol – pomegranate fruit peel, lemon balm leaves, cinnamon bark, and grape pomace – for their potential prebiotic activities and protective effects in a mouse model of mild intestinal inflammation. Methods : Mice received extracts orally for 4 weeks prior to colitis induction with dextran sulfate sodium. Results : All four extracts reduced colonic inflammation markers, and only grape pomace delayed disease onset. Extracts modified gut microbiota composition during colitis, differentially influencing the abundance of beneficial taxa, pathobionts, hydrogen sulfide producers, and mucus-associated species, such as Akkermansia muciniphila . Metabolomic analysis revealed extract-specific alterations in fecal metabolite profiles, particularly regarding levels of ethanol, glycine and amino acids. Colonic gene transcript profiling showed that grape pomace had the most beneficial effects on the expression of genes involved in epithelial barrier function, microbial sensing, inflammation signaling and innate immunity during colitis. Histological and imaging data further confirmed that grape pomace preserved tight-junction integrity and limited bacterial translocation during colitis. Conclusion : The findings demonstrate that the four polyphenol-rich extracts prevent colitis-induced intestinal damage, likely through modulation of gut microbiota, fecal metabolites and barrier function. Of them, grape pomace extract induced the most promising effect against colitis, combining improved clinical symptoms and restoration of host–microbiome homeostasis.