Fucoidan exerts antitumor effects by regulating gut microbiota and tryptophan metabolism

Fucoidan, a water-soluble polysaccharide derived from marine organisms, has garnered significant attention for its ability to regulate gut microbiota and its anti-tumor properties. However, the existence of a correlation between the anti-tumor effect of fucoidan and its regulation of the gut microbiota remains unknown. In pursuit of this objective, we culled the gut microbiota of mice with broad-spectrum antibiotics to generate pseudo-sterile tumor-bearing mice. Subsequently, fecal microbial transplants were introduced into the pseudo-sterile tumorbearing mice. The antitumor effects of fucoidan were found to be dependent on the gut microbiota. Fucoidan promoted the proliferation of Akkermansia, Bifidobacterium and Lactobacillus, which have immunomodulatory effects. Furthermore, through regulation of gut microbiota, fucoidan influenced the metabolic process of tryptophan and facilitated its conversion to indole-3-acetic acid. In addition, fucoidan decreased the kynurenine/ tryptophan ratio in serum, increased the proportion of CD8+ T cells, and suppressed the expression level of IDO1 in tumor tissues. Our results confirm that fucoidan enhances anti-tumor immune responses and subsequently exhibits anti-tumor effects by modulating the gut microbiota. Our research contributes to the comprehension of the mechanism of anti-tumor effects of fucoidan and facilitates the development of fucoidan as a dietary supplement for cancer patients.