Modulation of tryptophan metabolism via AHR-IL22 pathway mediates the alleviation of DSS-induced colitis by chitooligosaccharides with different degrees of polymerization.

Oral administration of chitooligosaccharides (COS) has been reported to alleviate colitis in mice. However, the mechanism of action of COS with specific polymerization degree on gut inflammation and metabolism remains unclear. This study aimed to investigate the effects of chitobiose (COS2), chitotetraose (COS4), and chitohexaose (COS6) on colitis, and to elucidate their underlying mechanisms. COS2, COS4, and COS6 were able to significantly alleviate colonic injury and inflammation levels. COS6 has the best anti-inflammatory effect. Furthermore, COS6 could down-regulate the level of indoleamine-2,3-dioxygenase1 (IDO1) and restore the levels of indole, indoleacetic-3-acid (IAA), and indole-3-carbaldehyde (I3A) in the cecum of chronic colitis mice (p < 0.05), thereby regulating tryptophan metabolism. In the aromatic hydrocarbon receptor-IL-22 (AHR-IL-22) pathway, although there were differences between chronic colitis and acute colitis mice, COS intervention could restore the AHR-IL-22 pathway to normal, promote the expression of MUC2, and repair the intestinal mucosal barrier. In conclusion, the results of this study suggested that COS had a good inhibitory effect on IDO1 under inflammation and the changes of AHR and IL-22 levels at different stages of disease development. This provides new insights into the potential use of COS as a functional food for improving intestinal inflammation and metabolism.