Myrica rubra juice attenuates DSS-induced colitis and is associated with changes in the gut...

Ulcerative colitis (UC) is characterized by chronic intestinal inflammation and impaired mucosal barrier function. Myrica rubra contains polyphenols and flavonoids, but the mechanisms underlying its potential protective effects in colitis remain unclear. We evaluated Myrica rubra juice (MRJ) in a dextran sulfate sodium (DSS)-induced mouse model of colitis and a TNF-α-injured colonic organoid model. The study combined 16S rRNA gene sequencing, untargeted serum and fecal metabolomics, and molecular docking. MRJ treatment attenuated disease severity and was associated with increased expression of occludin and MUC2 in DSS-treated mice. MRJ also altered microbial diversity and taxonomic composition in a taxon-specific manner. Serum and fecal metabolomic profiles differed after MRJ treatment, including pathways related to amino acid and bile acid metabolism. Integrated analyses identified associations among microbial taxa, putatively annotated metabolites, and host inflammatory and barrier-related variables. Direct exposure to 20% (v/v) whole MRJ increased occludin immunofluorescence in TNF-α-injured colonic organoids cultured without a gut microbial community. This single-marker result is consistent with an epithelial response to whole MRJ under the applied in vitro conditions. Molecular docking generated predicted poses and docking scores for selected parent compound-protein pairs. These calculations did not demonstrate physical binding, functional inhibition, or target engagement in vivo. Together, the findings support a direct epithelial response and identify concurrent microbiota-associated changes. However, the present design could not determine whether these microbial changes contributed to protection. It also could not separate or quantify the host-directed and microbiota-mediated contributions or identify the active chemical species.