Intestinal peristalsis, formed by the undulating contraction of the intestine, is an important part of the intestinal physical barrier. Following initial digestion in the stomach, food enters the small intestine, where it is absorbed by peristalsis. In a double-blind, randomized clinical trial, Matayoshi et al (8) reported that the administration of fucoidan (1 g/day) for 4 weeks significantly improved the number of defecations, the daily number of defecations, the soft and hard faeces index, and the volume of faeces in patients with constipation. The effect was more apparent in patients had taken fucoidan for 8 weeks. As a result, fucoidan from Nemacystus decipiens (Mozuku) can promote intestinal peristalsis, improve constipation, regulate the intestinal mechanical barrier (8).

The length of villi and the crypt depth of the small intestine are used to measure the digestive and absorption function of the small intestine, and the ratio of these indicates the comprehensive function of the small intestine. It was previously found that the daily administration of fucoidan extracted from Acaudina molpadioides improved the histological morphology of the small intestine damaged by cyclophosphamide and increased the villus length of the small intestine (9). The beneficial effect was more significant in the group treated with a molecular weight of 50 kDa of fucoidan. Fucoidan and its enzymatic hydrolysates, among which the 50 kDa fragment, exerted optimal effects in alleviating the weight loss caused by intestinal mucosal injury, and upregulating the expression of antibacterial peptides and stem cell marker genes. The mechanism responsible for its protective effects against chemotherapy-induced intestinal mucosal injury was found to be related to the Toll-like receptor-mediated MyD88 signalling pathway. In addition, fucoidan and its enzymatic hydrolysates also improved the villus/crypt ratio (V/C ratio; the ratio of the length of the villi and crypt depth of the small intestine) to varying degrees (9). Another study demonstrated that fucoidan increased the expression of intestinal tight junction proteins in a rat model of breast cancer, improving the structure of the intestine (10). The morphological structure of the intestine was significantly improved, and the damage to the intestinal mucosal physical barrier was also alleviated (10).

Researchers have found that the pathogenic mechanisms of intestinal physical barrier injury may be that the dysfunction of cellular signalling pathways destroys key genes of intestinal epithelial cell differentiation, and the increased the susceptibility of patients to inflammatory bowel disease may be related to a lack of Notch 1 signalling (11). Lin et al (12) observed the effects of fucoidan on lipopolysaccharides and constructed a cell model of inflammatory injury of human colon epithelial cells. Their results revealed that the cell survival rate of the fucoidan intervention group significantly increased, and was positively associated with the fucoidan medium concentration. Fucoidan also attenuated the decrease in intestinal cell proliferation rate induced by inflammatory injury and repaired damaged intestinal epithelial cells (12). Furthermore, the effect was concentration-dependent.

Researchers have found that fucoidan can stimulate the proliferation, differentiation and maturity of immunoactive cells, regulates the Th1/Th2 ratio of the intestinal helper T-cells, protects the intestinal immune barrier and reduce the body's inflammatory response, as evidenced by a series of scientific experiments (12). Shang et al (13) found that fucoidan reduced the antigen load of the body, relieved the inflammatory response of the host, increased the expression of immunoglobulin A (IgA) and reduced the level of serum lipopolysaccharide binding protein. O'Shea et al (14) established an experimental porcine model of colitis induced by dextran sodium sulfate (DSS), and conducted intragastric intervention with fucoidan to observe the effects of on the pathological changes of colitis. It was found that fucoidan increased the body weight, and improvised the proximal colon pathological score and diarrhoea score of the pigs, also reducing the abundance of IL-6 mRNA in the colon (14).

There is evidence to indicate that fucoidan regulates the expression of certain cytokines in the intestinal mucosa. Park et al (15) found that fucoidan enhanced the intestinal immune barrier and anti-inflammatory function by inhibiting the secretion of IL-1β, IL-13, TNF-α, IL-6, IFN-γ and other inflammatory factors by macrophages. It has been reported that the oral administration of fucoidan decreases the synthesis of pro-inflammatory cytokines and exerts protective effects on intestinal barrier function in non-obese diabetic mice (16). Fucoidan was also shown to enhance intestinal acquired immunity by increasing the expression of the IL-6 and IL-10 cytokines (7). In addition, through in vitro and in vivo experiments, it has also been found that fucoidan can directly interact with Toll-like receptors of immune cells to produce mucin and enhance the immune response (17).

Fucoidan can promote the activation of immune effector cells, regulate the intestinal immune barrier and improve the immune capacity of the body, thus playing an auxiliary therapeutic role in inhibiting intestinal tumours and alleviating the side-effects of chemotherapy. Usoltseva et al (5) found that fucoidan and its derivatives inhibited the growth of human colorectal adenocarcinoma epithelial cells and human colon cancer cells in in vitro cell experiments. It was found that fucoidan can play an anticancer role independently of the p53 gene, and can also cooperate with the p53 gene to exert anticancer effects (5). Chen et al (18) found that fucoidan inhibited the expression of endoplasmic reticulum protein-29 in colon cancer cells, promoted the expression of the apoptotic protein, Bax and induced the apoptosis of colon cancer cells.

Experimental studies have found that fucoidan can alter the structure, diversity and abundance of the intestinal flora, thus protecting intestinal microbial barrier function (10). Shi et al (9) found that the addition of fucoidan (50 mg/kg body weight) to the daily diet altered the intestinal flora of normal mice, increased the diversity of the flora, and significantly increased the number and abundance of probiotics, such as Coprococcus, Rikenellaceae and Butyricicoccus in the intestinal tract of mice. It also reduce the relative number and abundance of harmful bacteria, such as Proteobacteria, Firmicutes and Corynebacterium, thus attenuating intestinal mucosal injury (9).

A series of studies have suggested that fucoidan can be used as a microecological modulator in the adjuvant treatment of some diseases mediated by the intestinal flora (19). It has been found that fucoidan may be used as an intestinal microbiota regulator to promote health and to treat intestinal dysfunction, significantly reduce the host's antigen load and inflammatory response, and reduce the level of serum lipopolysaccharide binding protein (15). Liu et al (20) demonstrated that fucoidan extracted from Undaria pinnatifida significantly reduced the abundance of Staphylococcus in the intestinal tract, which was positively associated with dyslipidaemia, and also significantly increased the abundance of Prevotella, which was negatively associated with obesity. Chen et al (21) found that the supplementation of algae polysaccharide reduced the abundance and number of Corynebacterium, Brevibacterium and Aerococcus caused by a high-fat diet, and effectively restored the disruption of intestinal flora homeostasis induced by a high-fat diet in rats, and improve dyslipidaemia. It has also been found that the number of Akkermansia decreased significantly in pre-diabetic and diabetic patients, while the bacteria were significantly enriched following intervention with fucoidan in diabetic model mice; the decrease in the number Akkermansia was significantly improved, and metabolic disorders, such as insulin resistance were reversed (22). Another study using animal models proved that fucoidan derived from Laminaria Japonica significantly reduced weight gain, attenuated liver steatosis and alleviated inflammation (23). Further analysis of the mechanisms from the perspective of intestinal flora revealed that fucoidan enriched the beneficial bacteria, such as Alloprevotella, Akkermansia, Blautia and Bacteroidetes, and increased the production of short-chain fatty acids (SCFAs). SCFAs are ligands of G-protein-coupled receptors, which can affect insulin sensitivity in adipose tissue and peripheral organs, thereby regulating energy metabolism and reducing fat accumulation (23).