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.