Effects of fucoidan on gut flora and tumor prevention in 1,2-dimethylhydrazine-induced colorectal carcinogenesis

Xue, Meilan; Liang, Hui; Ji, Xinqiang; Zhou, Zhitong; Liu, Ying; Sun, Ting; Zhang, Li

doi:10.1016/j.jnutbio.2020.108396

Cited by 39 publications

(43 citation statements)

References 53 publications

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“…Nevertheless, most fucoidan share common bioactivities including anti-cancer, anti-inflammatory, anti-bacterial, anti-viral, and anti-HIV activities. Among these functions, the anti-cancer properties of fucoidan attracted considerable attentions ( Han et al, 2015 ; Atashrazm et al, 2016 ; Xue et al, 2020 ). Fucoidan has been observed to function as an antitumor agent in combination with conventional therapeutics in multiple models ( Jin et al, 2014 ; Hsu and Hwang, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Fucoidan-Supplemented Diet Potentiates Immune Checkpoint Blockage by Enhancing Antitumor Immunity

Yang

Pan

et al. 2021

Front. Cell Dev. Biol.

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Immune checkpoint blockade (ICB) therapies such as PD-1 antibodies have produced significant clinical responses in treating a variety of human malignancies, yet only a subset of cancer patients benefit from such therapy. To improve the ICB efficacy, combinations with additional therapeutics were under intensive investigation. Recently, special dietary compositions that can lower the cancer risk or inhibit cancer progression have drawn significant attention, although few were reported to show synergistic effects with ICB therapies. Interestingly, Fucoidan is naturally derived from edible brown algae and exhibits antitumor and immunomodulatory activities. Here we discover that fucoidan-supplemented diet significantly improves the antitumor activities of PD-1 antibodies in vivo. Specifically, fucoidan as a dietary ingredient strongly inhibits tumor growth when co-administrated with PD-1 antibodies, which effects can be further strengthened when fucoidan is applied before PD-1 treatments. Immune analysis revealed that fucoidan consistently promotes the activation of tumor-infiltrating CD8+ T cells, which support the evident synergies with ICB therapies. RNAseq analysis suggested that the JAK-STAT pathway is critical for fucoidan to enhance the effector function of CD8+ T cells, which could be otherwise attenuated by disruption of the T-cell receptor (TCR)/CD3 complex on the cell surface. Mechanistically, fucoidan interacts with this complex and augments TCR-mediated signaling that cooperate with the JAK-STAT pathway to stimulate T cell activation. Taken together, we demonstrated that fucoidan is a promising dietary supplement combined with ICB therapies to treat malignancies, and dissected an underappreciated mechanism for fucoidan-elicited immunomodulatory effects in cancer.

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Section: Introductionmentioning

confidence: 99%

Fucoidan-Supplemented Diet Potentiates Immune Checkpoint Blockage by Enhancing Antitumor Immunity

Yang

Pan

et al. 2021

Front. Cell Dev. Biol.

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“…For example, studies have shown that the gut microbiota plays a vital role in developing colon cancer in mice 86 . Xue et al 87 . reported that fucoidan treatment (400 mg kg −1 ) decreased the incidence of colorectal tumors and the mortality rate of rats with colorectal tumors.…”

Section: Colorectal Cancermentioning

confidence: 99%

“…Nondigestible dietary fiber (such as fucoidan) is metabolized by the colonic microbiota, producing large amounts of SCFAs 90 . Fucoidan increased the levels of butyric acid and valeric acid in 1,2‐dimethylhydrazine‐induced colorectal cancer rats, which could be used to enhance the ability of the microbiota to produce SCFAs 87 . Furthermore, SCFAs can also affect immune function.…”

Section: Colorectal Cancermentioning

confidence: 99%

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Metabolic regulation mechanism of fucoidan via intestinal microecology in diseases

et al. 2021

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The intestinal microecology is an extremely complex ecosystem consisting of gut microbiota, intestinal mucosa and the intestinal immune system. The intestinal microecology performs several important functions and is considered to be an essential ‘organ’ because it plays an important role in regulating human metabolism. Fucoidan contains a large amount of fucose and galactose residues, as well as various other neutral and acidic monosaccharides. Fucoidan particularly effects tumors, inflammatory bowel disease, diabetes and obesity by repairing intestinal mucosal damage and improving the intestinal microecological environment. It has been proposed that fucoidan could be used as a prebiotic agent for pharmaceutical and functional foods. In this review, we elucidate the potential mechanisms of the metabolic regulation of fucoidan with respect to the intestinal microecology of diseases. © 2021 Society of Chemical Industry

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“…Fucoidan was extracted from Fucus vesiculosus as described in our previous study (19). The fucoidan sample predominantly contained fucose (42.5%) and mannose (6.3%), and the content of sulfates was 32.1%.…”

Section: Fucoidan Preparationmentioning

confidence: 99%

Effect of fucoidan on ethanol-induced liver injury and steatosis in mice and the underlying mechanism

Xue

Liang

Zhou

et al. 2021

Food & Nutrition Research

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Background: Alcoholic liver disease is caused as a result of chronic alcohol consumption. In this study, we used an alcoholic liver injury mouse model to investigate the effect of fucoidan on ethanol-induced liver injury and steatosis and the underlying mechanisms. Methods: All mice were randomly divided into four groups: 1) control group, 2) model group, 3) diammonium glycyrrhizinate treatment group (200 mg/kg body weight), and 4) fucoidan treatment group (300 mg/kg body weight). Administration of ethanol for 8 weeks induced liver injury and steatosis in mice. Results: Fucoidan treatment decreased serum alanine aminotransferase activity, serum total cholesterol levels, and hepatic triglyceride levels, and improved the morphology of hepatic cells. Fucoidan treatment upregulated the expression of AMPKα1, SIRT1, and PGC-1α and inhibited the expression of ChREBP and HNF-1α. The levels of hepatic IL-6 and IL-18 were significantly decreased in the fucoidan group. Further, the levels of cytochrome P450-2E1 (CYP2E1), glucose-regulated protein (GRP) 78, and 3-nitrotyrosine (3-NT) in hepatic tissues were reduced in the fucoidan group as compared to the model group. Fucoidan significantly reversed the reduction of ileac Farnesoid X receptor (FXR) and fibroblast growth factor 15 (FGF15) levels induced by alcohol- feeding and reduced CYP7A1 (cholesterol 7α-hydroxylase) expression and total bile acid levels in the liver tissue. In addition, fucoidan regulated the structure of gut flora, with increased abundance of Prevotella and decreased abundance of Paraprevotella and Romboutsia as detected by 16S rDNA high-throughput sequencing. Conclusion: Fucoidan inhibited alcohol-induced steatosis and disorders of bile acid metabolism in mice through the AMPKα1/SIRT1 pathway and the gut microbiota–bile acid–liver axis and protected against alcohol- induced liver injury in vivo.

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Effects of fucoidan on gut flora and tumor prevention in 1,2-dimethylhydrazine-induced colorectal carcinogenesis

Cited by 39 publications

References 53 publications

Fucoidan-Supplemented Diet Potentiates Immune Checkpoint Blockage by Enhancing Antitumor Immunity

Fucoidan-Supplemented Diet Potentiates Immune Checkpoint Blockage by Enhancing Antitumor Immunity

Metabolic regulation mechanism of fucoidan via intestinal microecology in diseases

Effect of fucoidan on ethanol-induced liver injury and steatosis in mice and the underlying mechanism

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