Molecular weight-dependent therapeutic efficacy of guluronic alginate oligosaccharides in ulcerative colitis: insights into intestinal flora modulation and NF-κB pathway

Alginate oligosaccharides (AOS) exhibit structure-dependent anti-inflammatory bioactivities, yet their structural optimization for targeted therapy of ulcerative colitis (UC) remains underexplored. In this investigation, we prepared two enzymatically degraded guluronic-AOS (GAOS) with molecular weights of 1975 Da (named LGAOS, G/M = 5.98) and 5426 Da (named HGAOS, G/M = 10.69), and conducted a comprehensive analysis of their therapeutic effects in a dextran sulfate sodium (DSS)-induced UC mouse model. The results demonstrated that both GAOS compounds significantly attenuated the severity of UC, leading to a substantial amelioration of clinical symptoms. Moreover, our findings establish GAOS as potent microbiota-modulating agents for UC management, with higher molecular weight fractions showing enhanced therapeutic potential through multi-target regulation of inflammatory signaling, epithelial barrier function, and microbial metabolic networks. In general, this study elucidated the molecular mechanism underlying the anti-colitis effects of GAOS from the perspective of the microorganism-metabolism-immune regulation network, demonstrating the potential of GAOS in the treatment of ulcerative colitis.