Preventive effects of sea cucumber-derived fucoidan on Helicobacter pylori-induced gastritis: a mechanistic investigation based on regulation of the gut microbiota and metabolic products.

High-dose Fuc-SC significantly reduced H. pylori SS1 colonization in the gastric mucosa by approximately 18%.

• High-dose Fuc-SC was administered at 150 mg kg-1.
• Treatment significantly reduced levels of Hp SS1 immunoglobulin G (Hp-IgG) and cytotoxin-related gene A immunoglobulin G (CagA-IgG).
• Fuc-SC inhibited urease activity, contributing to reduced colonization.
• The reduction in Hp SS1 colonization in the gastric mucosa was approximately 18%.

Fuc-SC modulated oxidative stress more effectively than Fuc-LJ, suppressing NO, MDA, and ROS levels.

• Fuc-SC suppressed nitric oxide (NO), malondialdehyde (MDA), and reactive oxygen species (ROS).
• The superior antioxidant effect of Fuc-SC compared to Fuc-LJ was attributed to its smaller molecular weight and higher sulfate content.
• Both fucoidan sources were compared directly in the study design.

Fuc-SC dose-dependently regulated inflammatory cytokine expression in H. pylori-induced gastritis.

• Fuc-SC dose-dependently down-regulated IL-1β, IL-6, Th17 cells, IFN-γ, and TNF-α.
• Fuc-SC up-regulated the anti-inflammatory cytokine IL-10.
• These effects modulated expression of inflammatory protein S100A8 and E-cadherin in the gastric mucosa.
• The combined cytokine modulation resulted in alleviation of gastric inflammation.

Fuc-SC inhibited pathogenic bacteria and promoted beneficial probiotic populations as revealed by 16S rRNA analysis.

• Fuc-SC inhibited pathogenic bacteria including Dubosiella and Monoglobus.
• Fuc-SC promoted probiotics including Lactobacillus and Akkermansia.
• Gut microbiota composition was assessed using 16S rRNA analysis.
• Microbiota modulation was associated with mitigation of inflammatory responses.

Fuc-SC enhanced biosynthesis of short-chain fatty acids and beneficial metabolites as revealed by metabolomics analysis.

• Metabolomics analysis identified enhanced biosynthesis of short-chain fatty acids following Fuc-SC treatment.
• Beneficial metabolites promoted included naringenin, afzelechin, and pinocembrin.
• Metabolomics findings were interpreted in conjunction with 16S rRNA microbiota data.
• These metabolic changes were linked to the anti-inflammatory protective effects of Fuc-SC.