Red rice seed coat maintained intestinal homeostasis in mice by alleviating inflammation, improving barrier function and modulating gut microbiota dysbiosis

• RRP improved intestinal barrier function via CCR5/MMP9 pathway. • RRP attenuated inflammation through CCR5/NFκB pathway. • RRP ameliorated gut microbiota composition in colitis mice. • RRP could be a promising candidate for use as a functional food ingredient. Although red rice seed coat extract (RRP) contains various active ingredients that demonstrate some physiological benefits, its potential role in regulating intestinal homeostasis remains unknown. This work aims to evaluate the function of RRP in alleviating inflammation, modulating barrier function, and altering dysbiosis of the gut microbiota, to further reveal its potential mechanisms. The effects of RRP on intestinal homeostasis were assessed using histopathological examination, intestinal barrier integrity and gut microbiota composition. The potential targets of RRP were analyzed using multiple bioinformatics databases. Western blotting, immunofluorescence method, or detection kits were utilized to examine the effects of RRP on targets and corresponding pathways in model mice received 600 mg/kgbw (RRP-High dose, RRPH) and 200 mg/kgbw (RRP-Low dose, RRPL) of RRP. Our results revealed that RRP improved intestinal barrier function via chemokine C-C-primitive receptor 5 (CCR5)/ matrix metalloproteinase 9 (MMP9) pathways, attenuated inflammation through CCR5/ nuclear factor kappa B (NFκB) pathway, and ameliorated gut microbiota composition in model mice. In general, RRP treatment was found to maintain intestinal homeostasis in mice by alleviating inflammation, improving barrier function, and modulating dysbiosis of the gut microbiota. This suggests RRP could be a promising candidate for use as a functional food ingredient.