Sea Cucumber Fucoidan Inhibits <i>Helicobacter pylori</i> Gastritis via MAPK/NF-κB Signaling and Gut Microbiota Modulation

Antibiotic-based eradication therapy for<i>Helicobacter pylori</i> faces challenges such as the increasing number of antibiotic-resistant strains and gut microbiota dysbiosis. The study evaluated the effects of fucoidan from sea cucumber cooking liquid (Fuc-SC) on <i>Helicobacter pylori</i> <i>Sydney strain SS1</i> (Hp SS1)-associated gastritis. The backbone structure of Fuc-SC was composed of alternating → 3)-α-L-Fuc<i>p</i>-(1 → 4)-α-L-Fuc<i>p</i>-(1 → linked fucose residues. The mouse experiments demonstrated that Fuc-SC reduced the colonization of Hp SS1 in the gastric mucosa through decreasing the level of urease, Hp-IgG, and CagA-IgG. In addition, Fuc-SC regulated oxidative stress levels by reducing NO, MDA, and ROS levels, while increasing the activity of SOD and GSH-Px. Compared to antibiotic treatment alone, the combination of Fuc-SC with antibiotics further enhanced the antioxidant effects. Molecular mechanisms indicated that Fuc-SC regulated the MAPK/NF-κB signaling pathway, downregulating the expression of inflammatory factors such as IL-1β and TNF-α and further modulating the expression of S100A8 and E-cadherin. Gut microbiota analysis indicated that Fuc-SC reversed the depletion of <i>Lactobacillus</i> caused by antibiotic treatment. Additionally, Fuc-SC significantly promoted the biosynthesis of microbial metabolites such as butyric acid, isobutyric acid, hexanoic acid, and phospholipids, thereby alleviating inflammation. These findings highlight its potential as a sustainable, nonantibiotic therapy for <i>Helicobacter pylori</i>-associated gastritis.