Multi-omics analysis reveals that agaro-oligosaccharides with different degrees of polymerization alleviate colitis in mice by regulating intestinal flora and arginine synthesis

Inflammatory bowel disease (IBD) is a common chronic disease with a complex etiology, characterized by body weight loss, intestinal barrier damage, and an imbalance of intestinal flora, posing a significant threat to people's health. In this work, we studied whether safer natural active agaro-oligosaccharides (AOSs) benefit mice with IBD and elucidated their underlying mechanisms. The findings indicated that oral administration of agarobiose (A2), agarotriose (A3), and agarotetraose (A4) contributed to alleviating body weight loss and colon shortening, as well as enhancing IL-10 levels while reducing IL-6, IL-1β, and TNF-α. AOSs improved colon disruption, reduced the number of goblet cells caused by DSS, and enhanced the expression of Muc2, ZO-1, and occludin-1 to repair the intestinal barrier. It is noteworthy that A3 demonstrated superior outcomes in the evaluated AOSs relative to A2 and A4. This was evidenced by an increase in Bacteroidota and reduced Firmicutes at the phylum level, which corrected DSS-induced intestinal dysbiosis and significantly restored disrupted metabolic pathways, including amino acid and lipid metabolism. The differential metabolites between the AOS treatment groups and the model group were mainly enriched in arginine synthesis with co-regulated critical substances N-acetyl-L-citrulline and N2-acetylornithine, which alleviated colitis. This evidence offers a fresh perspective on the potential application of AOSs as functional foods to improve intestinal inflammation and metabolism.