Hyaluronic Acid-Melatonin Nanoparticles Improve the Dysregulated Intestinal Barrier, Microbiome and Immune Response in Mice with Dextran Sodium Sulfate-Induced Colitis

Although the cause of inflammatory bowel disease (IBD) is unclear, current studies have found that the main factors involved in its pathogenesis include imbalance of mucosal immune response, intestinal dysbiosis, and destruction of the intestinal barrier. We synthesized an amphiphilic conjugate of hyaluronic acid (HA) and melatonin (MT), which have established immunomodulatory and antioxidant properties, by stimulating their nano-aggregation. Inducing colitis by dextran IP: 182 75 148.10 On: Tue, 22 Feb 2022 12:40:40 sodium sulfate (DSS), HA-MT accumulated in te inflamed colon epithelium of colitis mice, and markedly improved the Copyright: American Scientific Publishers colitis symptoms, repaired the damaged intestinal barrier andinhibited colon inflammation. In addition, through bacteDelivered by Ingenta rial 16S rDNA sequencing, it was found that HA-MT can restore the ratio of Firmicutes/Bacteroidetes by increasing the overall microbial richness and diversity, and alleviate the intestinal dysbiosis of mice with colitis. In the analysis of the intestinal flora at the species level, the abundance of Lactobacillus increased in colitis mice treated with HA-MT while that of Bacteroides, Blautia and Streptococcus decreased in the colitis mice treated with HA-MT. Our findings suggest that the HA-MT system is a promising prebiotic, which can relieve the symptoms of IBD by regulating the intestinal microflora and restoring intestinal homeostasis, inhibiting inflammation.