Therapeutic Potential of Polyphenols in Targeting Th17/Treg Balance for Intestinal Barrier Maintenance

The integrity of the intestinal barrier is essential for overall health. Disruption of tight junction (TJs) proteins negatively affects intestinal barrier function, leading to immune imbalances and causing a variety of pathological conditions that are closely associated with the pathogenesis of multiple diseases. Th17 and Treg cells are two distinct phenotypes of CD4⁺ T cells with opposing functions. The balance established between these two subpopulations is essential to prevent the development of disease. Emerging evidence suggests that the Th17/Treg balance is an important potential target for improving the intestinal barrier. However, there is still a lack of effective drugs for the treatment of intestinal barrier dysfunction or disorders. Polyphenols, natural compounds found in plants, have gained attention as potential therapies. Research shows that polyphenols can regulate the Th17/Treg balance by influencing key molecular pathways, such as NF-κB, MAPK, aryl hydrocarbon receptor (AhR), and peroxisome proliferators activate receptors-γ (PPARγ), while also improving gut microbiota. These actions help increase TJ protein levels, reduce gut permeability, and lower inflammation. Preclinical and clinical studies suggest that polyphenols may help treat conditions like inflammatory bowel disease (IBD) by restoring gut health and immune balance. In the present review, we highlight how the Th17/Treg balance affects intestinal permeability, and recent findings regarding possible effects and the molecular mechanism of polyphenols in regulating the Th17/Treg balance, to provide new potential therapeutic strategies for damaged intestinal barrier treatment preclinically and clinically.