The Role of Seaweed Polysaccharides in Gastrointestinal Health: Protective Effect against Inflammatory Bowel Disease

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TL;DR

This systematic review examines the therapeutic potential of seaweed-derived polysaccharides (fucoidan, ulvan, carrageenan, laminarin) for treating inflammatory bowel disease (IBD). The authors found that algal polysaccharides can target multiple IBD pathways, including reducing pro-inflammatory cytokines, improving intestinal barrier function, modulating gut microbiota, and blocking adhesion molecules. While preclinical evidence is promising, the review highlights a critical gap in clinical trials and emphasizes the need for further human studies to establish safety and efficacy.

Full summary

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**Background:** Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory condition of the gastrointestinal tract with complex etiology involving genetic predisposition, epithelial barrier dysfunction, dysregulated immune responses, and environmental factors. Current treatments including anti-inflammatory drugs (corticosteroids), immunosuppressants (thiopurine, calcineurin inhibitors), and biological therapies are often associated with severe adverse effects such as obesity, hypertension, diabetes, moon face, and weakened immunity with long-term use. Marine seaweeds contain high amounts of sulfated polysaccharides that resist gastric digestion and can serve as fermentation substrates for beneficial gut microbes, making them promising candidates for IBD therapy.

**Methods:** The authors conducted a comprehensive search of PubMed, Scopus, and Web of Science using keywords including "seaweed", "polysaccharides", "inflammatory bowel disease", "ulcerative colitis", and "Crohn's disease". Manual reference list searches were also performed. Studies examining the effect of polysaccharides on IBD in humans and animals were included; studies focusing on other seaweed components were excluded. Data were synthesized using a narrative approach involving summarization of findings and pattern recognition.

**Key Results:** The review identified multiple therapeutic mechanisms of algal polysaccharides against IBD:

1. **Adhesion molecule inhibition:** Fucoidan binds to P-selectin, suppressing neutrophil discharge into the abdominal cavity in rats with experimental peritonitis (Semenov et al., 1999). Intravenous fucoidan reduced colonic mucosal injury and crypt damage in DSS-induced mice by abolishing venular leukocyte rolling.

2. **Intestinal epithelial protection:** Fucoidan dose-dependently increased transepithelial resistance and protected intestinal epithelium from paracellular permeability while increasing claudin-1 expression. *Laminaria japonica* improved intestinal barrier function and prevented tight-junction-related protein inhibition while downregulating IL-6 and nitric oxide levels.

3. **Cytokine modulation:** Laminarin and fucoidan combination treatment prevented weight loss and diarrhea in DSS-treated pigs while downregulating IL-6 expression. *Eucheuma cottonii* polysaccharides downregulated TNF-α, IL-1β, IL-6, and IL-10 in DSS-induced mice. Fucoidans from *Kjellmaniella crassifolia* and *Cladosiphon okamuranus* reduced IL-6 production in CMT-93 cells and decreased NF-kB nuclear translocation. β-glucan from *Laminaria hyperborean* and *L. digitata* decreased Th-17-associated cytokines (IL-17a, IL-17F, IL-22) and IL-23R and IL-6 receptor expression.

4. **Gut microbiota modulation:** Fucoidan from *Fucus evanescens* increased growth and biomass accumulation of bifidobacteria. Oral fucoidan from *Ascophyllum nodosum* and *L. japonica* increased abundance of *Lactobacillus* and *Ruminococcacea* while reducing blood lipopolysaccharide-binding protein levels. Fermentation of sulfated polysaccharides from *Enteromorpha prolifera* and *L. japonica* increased short-chain fatty acids (acetic, butyric, lactic acids).

5. **Drug delivery systems:** Fucoidan–chitosan nanoparticles demonstrate pH-responsive profiles that prevent degradation in gastric acid. Selenium nanoparticles coated with *Ulva lactuca* polysaccharide (ULP-SeNPs) significantly reduced body weight loss and colonic inflammatory damage in DSS-induced acute colitis mice, with reduced plasma TNF-α, IL-6, COX-2, and iNOS levels through blocking NF-κB nuclear translocation.

**Clinical Implications:** Algal polysaccharides demonstrate significant potential as complementary IBD therapy through multiple mechanisms including anti-inflammatory effects, intestinal barrier protection, and prebiotic activity. Their low toxicity, biodegradability, and biocompatibility make them safe as food ingredients. However, the review identifies critical limitations: the majority of studies are ex vivo or animal trials with no clinical trials in humans with IBD. Most studies compared polysaccharides to placebo/control rather than standard treatments. Further research is needed to establish safety and efficacy in humans, compare effectiveness to standard therapies, and fully understand mechanisms of action.