Dietary Flavonoids and the Intestinal Mucus Barrier: Microbiota-Mediated Mechanisms and Future Perspectives

The intestinal mucus barrier is vital for gut homeostasis, and its dysregulation is a key driver of intestinal disorders. Although dietary flavonoids have garnered increasing attention for their capacity to fortify the intestinal mucus barrier, a systematic synthesis of their underlying mechanisms, particularly through their interactions with the gut microbiota, remains lacking. This review comprehensively summarizes the composition, regulation, and dynamic turnover of the intestinal mucus barrier, with emphasis on the central role of gut microbiota in its modulation. Critically, we examine the efficacy of six major flavonoid subclasses (flavones, flavonols, flavanones, isoflavones, flavan-3-ols, and anthocyanins) in reinforcing the mucus barrier and systematically outline their mechanisms of action. These mechanisms include reshaping microbial communities, enriching protective metabolites (e.g., short-chain fatty acids, tryptophan derivatives, and secondary bile acids), attenuating oxidative stress, suppressing inflammation, alleviating metabolic stress, and strengthening tight junctions to optimize mucus synthesis and maintenance. To translate these findings into effective clinical strategies, future research should integrate physiologically relevant mucus models, multi-omics approaches, and precision nutrition frameworks. This review provides a systematic reference for understanding how dietary flavonoids and their gut microbial metabolites coordinately fortify the intestinal mucus barrier, informing the development of targeted nutritional interventions for gut health.