Fucoidan is a polysaccharide—specifically a fucose-containing sulfated polysaccharide (FCSP)that constitutes 5% to 20% of the dry weight of algae. Previous studies have demonstrated that fucoidan possesses various biological activities, including antioxidant, anticoagulant, antithrombotic, anti-inflammatory, antiviral, hypolipidemic, anti-metastatic, antidiabetic, and anticancer effects. Dietary fucoidan provides a continuous supply of FCSPs to the intestinal tract. This process facilitates the reorganization of the resident gut microbiota—the composition of which has been altered by FCSPs—thereby enabling the suppression of inflammatory symptoms within the intestines. However, regarding the biological activities of fucoidan, current evidence substantiating its specific effects on the gut microbiota and intestinal health remains limited. Therefore, in this blog post, I would like to introduce the study titled “Fucoidans and Bowel Health” by Jin-Young Yang et al. This study reviews recent research highlighting the fundamental properties of various types of fucoidan. It discusses their potential to alter the composition of the resident microbiota, thereby influencing intestinal health and disease.
In addition to absorbing nutrients, the gastrointestinal tract plays a pivotal role in maintaining intestinal immunity by distinguishing between “beneficial” and “harmful” foreign antigens and by facilitating their interactions with various intestinal cells. In this study, we investigate the effects of fucoidan on both non-immune and immune cells within the gut.
The intestinal epithelial barrier is composed of a diverse array of cell types—including enterocytes, goblet cells, Paneth cells, and enteroendocrine cells—all of which originate from pluripotent intestinal stem cells (ISCs). Lgr5-positive ISCs can specifically recognize digested fructose and subsequently differentiate into either absorptive or secretory progenitor cells. Furthermore, the intake of carbohydrates and proteins has been shown to facilitate the repair and improvement of intestinal epithelial damage by enhancing membrane permeability. Intestinal epithelial cells are arranged to cover the epithelial surfaces of both the small and large intestines, and they are interconnected by tight junctions. These cells are known to interact with various nutrients—including polysaccharides—through mechanisms involving antigen uptake and endocytosis. In a separate study, it was demonstrated that fucoidan extracted from *Sargassum cinereum* (a species of *Sargassum* seaweed) inhibited the proliferation of Caco-2 cells, a colon cancer cell line. Caco-2 cells exhibit characteristics similar to those of intestinal epithelial cells, such as the ability to form an epithelial cell monolayer featuring a brush border structure. Additionally, a study utilizing HT-29-luc cells—which possess properties resembling those of human intestinal epithelial cells—investigated the effects of an extract derived from *Undaria pinnatifida* (wakame seaweed); compared to a control group, the treated cells exhibited enhanced superoxide anion radical scavenging activity and improved cell viability. Other studies employing the Caco-2 cell line have demonstrated that eggshell membrane proteins encapsulated within chitosan/fucoidan nanoparticles effectively reduced both nitric oxide (NO) production and the gene expression levels of TNF-α and IL-6, while simultaneously enhancing the paracellular permeability of fluorescein isothiocyanate-dextran across the intestinal epithelial cells (IECs).These results suggest that, in order to maximize the efficacy of fucoidan extracts with respect to immune responses, it is crucial to enhance their bioavailability. Furthermore, studies conducted in mice have revealed that fucoidan extracts can prevent the onset of cryptosporidiosis by inhibiting the adhesion of *Cryptosporidium parvum* oocysts to intestinal epithelial cells. These findings demonstrate that fucoidan can exert cytotoxic (anti-cellular) effects, thereby suggesting its potential applicability in cancer prevention. In a mouse study, it was reported that mucin secretion by mucous cells (goblet cells) increased significantly in the ileum and feces of mice harboring a mutation in the TNF Receptor-Associated Factor 3 Interacting Protein 2 (*Traf3ip2*) gene, following their consumption of a diet containing fucoidan derived from *Cladosiphon okamuranus* (Okinawa mozuku); this observation suggests a protective role for fucoidan against psoriasis.
Recent studies have demonstrated that dietary components can also influence the differentiation of intestinal progenitor cells. Lgr5-positive (Lgr5+) intestinal stem cells (ISCs) specifically recognize digested fructose, subsequently differentiating into either absorptive progenitor cells (i.e., intestinal epithelial cells) or secretory progenitor cells (i.e., tuft cells, goblet cells, and Paneth cells), respectively. Furthermore, it has been reported that the intake of carbohydrates and proteins can repair and ameliorate damage to the intestinal epithelium by enhancing membrane permeability. Intestinal epithelial cells are arranged to cover the epithelial surfaces of both the small and large intestines, and they are interconnected by tight junctions. These cells are known to interact with various nutrients, including polysaccharides—through mechanisms such as antigen uptake and endocytosis. In another study, it was demonstrated that fucoidan extracted from *Sargassum cinereum* (a species of *Sargassum* seaweed) inhibited the proliferation of Caco-2 cells, a colon cancer cell line. Caco-2 cells possess characteristics similar to those of intestinal epithelial cells, such as the ability to form an epithelial monolayer featuring brush-border structures [25]. Additionally, a study utilizing HT-29-luc cells—which resemble human intestinal epithelial cells—investigated the effects of an extract derived from *wakame* (*Undaria pinnatifida*); compared to a control group, the treated cells exhibited enhanced superoxide anion radical scavenging activity and improved cell viability. Other studies employing the Caco-2 cell line have shown that eggshell membrane proteins encapsulated within chitosan/fucoidan nanoparticles effectively reduced nitric oxide (NO) production as well as the expression levels of inflammatory cytokines such as TNF-α and IL-6. Concurrently, it has been confirmed that this protein enhances the paracellular permeability of fluorescein isothiocyanate-dextran in intestinal epithelial cells (IECs); this finding suggests that enhancing bioavailability is crucial for maximizing the efficacy of fucoidan extracts in modulating immune responses. Furthermore, studies utilizing mice have revealed that fucoidan extracts can prevent the onset of cryptosporidiosis by inhibiting the adhesion of *Cryptosporidium parvum* oocysts to intestinal epithelial cells. These findings demonstrate that fucoidan may play a role in cytotoxicity (anti-tumor activity), thereby suggesting its potential applicability in cancer prevention. In a mouse study, a significant increase in mucin secretion by mucous cells (goblet cells) was observed in the ileum and feces of mice harboring a mutation in the TNF receptor-associated factor 3-interacting protein 2 (*Traf3ip2*) gene, following their consumption of a diet supplemented with fucoidan derived from *Cladosiphon okamuranus* (Okinawa mozuku). This result suggests a protective role for fucoidan against psoriasis.
Fucoidan has also been reported to modulate the number and function of immune cells. In one study, immunohistochemical techniques were employed to identify fucoidan-positive cells and their specific cell types within the small intestines of rats fed a diet containing 2% fucoidan. Cells staining positive for both fucoidan and ED1 (a macrophage marker) were detected, suggesting that intestinal macrophages are likely the primary cell type responsible for internalizing fucoidan. Furthermore, recent studies have demonstrated that fucoidan treatment influences both the intracellular production of reactive oxygen species and the migration of macrophages and neutrophils in LPS (lipopolysaccharide)-stimulated murine macrophage cell lines (RAW 264.7) and zebrafish larvae. Regarding dendritic cells (DCs), it was observed that bone marrow-derived DCs from non-obese diabetic (NOD) mice fed fucoidan exhibited significantly reduced expression of MHC Class II and CD86 compared to a control group. This suggests that fucoidan maintains DCs in an immature state, thereby inducing immune tolerance in these mice. Moreover, fucoidan was found to inhibit the nuclear translocation of nuclear factor (NF)-κB p52 in B cells, while simultaneously promoting the proliferation of murine B cells during a 48-hour culture period following co-stimulation with interleukin (IL)-4 and anti-CD40 antibodies. These findings suggest that fucoidan may play a protective role against immunoglobulin (Ig) E-mediated diseases. In the spleens of mice fed high-molecular-weight fucoidan, a significant increase in CD8+ T cells and a corresponding decrease in the CD4+/CD8+ T-cell ratio were observed compared to the control group. This suggests that dietary fucoidan may have the potential to enhance cytotoxic T-cell responses. Separately, another research group found that when peripheral blood mononuclear cells isolated from patients with bronchial asthma were treated with oligo-fucoidan, the populations of Th1 and Treg cells expanded, and IL-10 production increased compared to a control group. This suggests that fucoidan may exert anti-inflammatory effects. Furthermore, studies using mice revealed that fucoidan enhances the expression of CD40, CD80, CD86, IL-6, IL-12, and TNF-α in splenic dendritic cells (DCs) and promotes the proliferation of CD4+ and CD8+ T cells. These results indicate that fucoidan can activate Th1 immune responses. In a recent study utilizing the human monocytic cell line U937, it was demonstrated—in a dose-dependent manner—that a fucoidan extract derived from *Fucus vesiculosus* L. exhibits greater inhibitory activity against p38 MAPK than the potent p38 MAPK inhibitor SB203580, and also exerts stronger inhibitory effects on COX-2 enzyme activity than the synthetic non-steroidal anti-inflammatory drug (NSAID) indomethacin. Additionally, Ruslan Medzhitov of Yale University recently demonstrated transcriptional changes in γδ T cells induced by a high-carbohydrate diet. It is hypothesized that the regulatory functions of these cells modulate carbohydrate-related transcriptional programs, including those governing monosaccharide transporters—by controlling IL-22 production. Taken together, these findings suggest that dietary nutrients such as fucoidan may alter the population composition of intestinal immune cells, including macrophages, dendritic cells (DCs), B cells, and T cells.
Fucoidan extracted from brown algae can exert beneficial effects on the host’s intestinal environment by altering the composition of the symbiotic microbiota. Wakame (*Undaria pinnatifida*) is rich in *Bifidobacterium longum*—a well-known prebiotic that influences host metabolic disorders by enhancing the intestinal absorption of Glucagon-like Peptide-1 (GLP-1). Mice administered fucoidan derived from *Ascophyllum nodosum* exhibited a higher relative abundance of *Lactobacillus* species, which regulate several processes related to host intestinal immunity, such as the regeneration of intestinal epithelial cells. Furthermore, mice administered dietary fucoidan showed increased levels of the *Ruminococcaceae* family—major producers of short-chain fatty acids (SCFAs)—which maintain intestinal homeostasis by modulating Th1 and Treg cells [87, 88]. Mekabu-derived fucoidan can inhibit the attachment and colonization of *Cryptosporidium parvum* on the intestinal epithelium in both humans and neonatal mice by directly binding to functional mediators produced by the pathogen. Other studies suggest that fucoidan extracted from *Cladosiphon okamuranus* also improves intestinal mucosal immunity by increasing the secretion of mucin and IgA into the intestinal lumen. These findings suggest that dietary fucoidan may serve as a key trigger for compositional changes in the gut microbiota, thereby influencing the maintenance of intestinal homeostasis.
Based on the foregoing, it is anticipated that this work will lead to a deeper understanding of the mechanisms by which fucoidan—when utilized as a food additive or dietary supplement—exerts its effects within the intestinal tract, and that it will contribute to the development of diet-based therapeutic strategies for intestinal diseases.
Source: Mar Drugs. 2021 Jul 30;19(8):436. doi: 10.3390/md19080436