Background and Objective: Helicobacter pylori (H. pylori) is a major causative agent of chronic gastritis, peptic ulcers, and gastric cancer. Its high global infection rate, compounded by rising antibiotic resistance, poses a persistent threat to public health. Therefore, discovering safe and effective natural compounds with anti‑H. pylori activity is a critical goal in functional food and pharmaceutical development. Marine-derived fucoidans, especially those from sea cucumbers, have attracted growing interest due to their unique sulfated structures and diverse bioactivities. In this study, a sulfated polysaccharide was first prepared from sea cucumber. Its inhibitory activity against H. pylori was then evaluated both in vitro and in vivo, which enabled a preliminary assessment of the anti-H. pylori potential of the sea cucumber-derived polysaccharides. Based on these, it was further purified to yield a fucoidan. Subsequent studies were conducted to explore its anti-H. pylori activity, as well as its regulatory effect on the gut microbiota during H. pylori infection, thereby systematically investigating the inhibitory efficacy of sea cucumber fucoidan against H. pylori infection.
Methods: In vitro antibacterial activity was assessed by determining the minimum inhibitory concentration (MIC₅₀). In vivo, a mouse model of H. pylori infection was established; histopathological staining, serum cytokine measurement, and 16S rRNA gene sequencing were employed to evaluate the effects of sea cucumber-derived polysaccharides on gastric lesions, inflammatory responses, and intestinal microbial ecology.
Results: The sulfated polysaccharide consisted mainly of fucose (58 mol%). It showed concentration‑dependent inhibition against H. pylori in vitro. In vivo, it ameliorated gastric erosions, haemorrhage and inflammatory infiltration, and exhibited both preventive and therapeutic effects. After purification, the fucoidan (fucose, 82 mol%) exhibited significantly stronger antibacterial activity. It reduced gastric mucosal damage and inflammatory cell infiltration, and suppressed serum levels of inflammatory cytokines such as TNF‑α. Microbiota analysis revealed that the fucoidan restored the relative abundances of Bacillota and Bacteroidota. α and β- diversity analyses indicated that it not only increased species richness and evenness but also promoted a more balanced and stable gut microbial community, suggesting a comprehensive reconstruction of intestinal microecology.
Conclusion: This study successfully prepared a structurally well‑defined fucoidan from sea cucumber with potent anti‑H. pylori activity. It exerted multifaceted benefits by alleviating gastric pathology, attenuating systemic inflammation, and favourably reshaping the gut microbiota. These findings provide a scientific basis for developing fucoidan‑based functional foods against H. pylori infection and broaden the application prospects of marine bioactive polysaccharides in gastrointestinal health.
 

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