Intrarectal xyloglucan administration reduces disease severity in the dextran sodium sulfate model of mouse colitis

Abstract

Background: The pathophysiology of inflammatory bowel diseases remains poorly under-stood and treatment remains suboptimal for many patients. We hypothesize that the inflammatory milieu secondarily prolongs the injury and attenuates healing. We propose primary or adjuvant therapy with biocompatible adhesives to restore a barrier to protect submucosal structures, particularly stem cells. Methods: We used the well-described mouse dextran sodium sulfate (DSS) model of colitis resembling human ulcerative colitis to test the therapeutic efficacy of intrarectal administration of the tamarind plant-derived xyloglucan (TXG) polymer adhesive which underwent extensive analytic characterization. Mice in control, DSS-only, TXG-only, and DSS + TXG groups were studied for gross (weight, blood in stool, length of colon) and multiple histologic parameters. Results: Compared to DSS-only mice, TXG prevented the weight loss, occurrence of blood in the stool and colon shortening, with all those parameters not being statistically different from treatment naïve animals. Histologically, there was dramatic and highly statistically significant reduction in the total inflammatory index and protection from goblet cell loss, cellular infiltration, crypt abscess formation, epithelial erosion, granulation tissue, epithelial hyperplasia crypt irregularity and crypt loss. The TXG purity and characterization were established by nuclear magnetic resonance, infrared spectroscopy, differential scanning calorimetry, and texture analysis. Conclusion: The striking attenuation of disease severity by intrarectal TXG use warrants future investigations of natural bioadhesives with well-established high safety profiles, and which could potentially be derivatized to include therapeutically active moieties for local drug delivery.