Solid Dispersion of Hesperidin Alleviates Acetic Acid-Induced Colitis Through Modulating the Gut Microbiota Dysbiosis in Rats

Hesperidin (HD) is predominantly found in citrus fruits, and has been shown to possess various biological properties, such as anti-inflammatory, antioxidant, and anti-carcinogenic. However, its application is limited by poor solubility. In this study, a new solid dispersion (SD) of hesperidin was prepared by ball milling using PVPK30 as the carrier, and the in vitro and in vivo studies and the therapeutic effects about colitis in rats were evaluated. In vitro analysis revealed that the solid dispersion showed a better release effect. The cumulative release of HD-SD reached 48.24% at 120 min, which was 5.9 times that of pure HD. In vivo studies demonstrated that C_max and AUC₀_-₂₄ were significantly higher in HD-SD compared with pure HD (<i>p</i> < 0.01), which were 2.67 and 1.50 times that of HD, respectively. Furthermore, treatment with HD-SD significantly alleviates symptoms and histological features in acetic acid (AA)-induced colitis in rats. Furthermore, HD-SD treatment significantly ameliorated the disease severity of acetic acid (AA)-induced colitis in rats, as evidenced by improved clinical signs, attenuated histological damage, and decreased levels of inflammatory factors (TNF-α, IL-6, and IL-1β). Moreover, the structure and relative abundance of the gut microbiota were modulated. Specifically, the relative abundance of <i>Erysipelotrichaceae</i> was decreased and the relative abundance of <i>Bacteroidota</i>, <i>Lachnospiraceae</i>, and <i>[Eubacterium]_coprostanoligenes_group</i> were increased. These results suggest that HD-SD could serve as a gut-health-promoting functional ingredient, potentially contributing to the dietary management of colitis through microbiota modulation.