Effect of fucoidan molecular weight on gut microbiota composition and anti-inflammatory activity after in vitro dynamic digestion and fermentation

Fucoidan, a marine-derived polysaccharide, exhibits antioxidant, anti-inflammatory, and prebiotic properties. Here, native fucoidan from Laminaria japonica (LJF) and its low-molecular-weight derivative (DLJF) were evaluated using an in vitro dynamic human gastrointestinal model, followed by human fecal fermentation. The results demonstrated that both LJF and DLJF maintained structural stability during digestion, with slight molecular weight (Mw) reduction and unchanged functional groups. Scanning electron microscopy revealed increased porosity post-digestion, while monosaccharide analysis confirmed that fucose, galactose, glucose, and glucuronic acid remained unchanged. Antioxidant activity improved after digestion, particularly in DLJF. Fermentation showed that LJF and DLJF modulated the gut microbiota, enhancing beneficial bacteria levels such as Bacteroides , Parabacteroides , and unclassified Lachnospiraceae , while promoting the production of short-chain fatty acids (SCFAs). DLJF was more rapidly utilized, elevating acetic, propionic, and butyric acid levels to 1.41, 2.20, and 1.54 times those of the control group, respectively, after 48 h of fermentation. Furthermore, the fermentation supernatants suppressed the secretion of pro-inflammatory cytokines in LPS-induced RAW264.7 macrophages. Notably, DLJF-F reduced IL-6, IL-1β, and TNF-α levels by 65.56 %, 77.69 %, and 62.02 %, respectively. These findings suggest that the lower-Mw fucoidan of was more readily fermented, effectively modulating gut microbiota and showing potential as a functional food ingredient for gut and immune health.