Accumulating evidences have reported that the gut microbiota plays an important role in the occurrence and progression of colorectal cancer. Commonly known as a kind of constituent macromolecules, non-digestible polysaccharides have always been fermented by the intestinal microbiota. Nostoc commune Vaucher (N. commune) has always been appreciated as a healthy food and supplementation worldwide as it is rich in nutrients. Particularly, polysaccharides account for 60% of the dry weight of N. commune. In this study, we examined the protective effects of the polysaccharides isolated from N. commune (NVPS) against colitis-associated colon tumorigenesis in mice treated with azoxymethane (AOM) and dextran sulfate sodium salt (DSS) and the impact of these polysaccharides on the intestinal microbiota. NVPS were administered to mice through an intragastric gavage for 14 weeks. Our results demonstrated that the treatment with NVPS significantly decreased the number and sizes of tumors and reduced the incidence of intestinal tumors. Using 16S rRNA gene sequencing and qPCR, we analyzed the bacterial composition of the fecal samples obtained from mice. The results demonstrated that the alterations in the abundance of Firmicutes and Bacteroidetes caused by the AOM/DSS treatment were significantly reversed in response to the NVPS treatment. Moreover, the short-chain fatty acid (SCFA)-producing genera, including butyric acid-producing genera (Butyricicoccus, Butyrivibrio and Butyricimonas) and acetic acid-producing genera (Lachnospiraceae UCG 001, Lachnospiraceae UCG 006, and Blautia), were drastically enriched following the NVPS intervention. These compositional alterations induced by the NVPS were associated with the suppressed colonic inflammation and carcinogenesis. In conclusion, our results demonstrated an appreciable capability of NVPS to restore the gut microbiota profile altered by AOM/DSS, indicating the potential of NVPS as a promising prebiotic candidate for the prevention and treatment of colorectal cancer.

The fruiting bodies of Hericium erinaceus (Bull.) Pers. are commonly used in China in the treatment of digestive system diseases. In this work, the polysaccharides from the fruiting bodies of Hericium erinaceus (HEFPs) were extracted, and their effects on human colorectal cancer cells (HCT-116 and DLD1) were investigated in vitro. Our results showed that HEFPs were mainly composed of arabinose, galactose, glucose, and mannose at a molar ratio of 8.99 : 11.15 : 1.2 : 1.97. They significantly inhibited the growth of these cells by inducing apoptosis by the modulation of Bax and Bcl-2 expression, which in turn induced the loss of mitochondrial membrane potential, leading to the activation of cleaved-caspase-9 and cleaved-caspase-3. These results suggested that HEFPs induced apoptosis via the caspase-9-depedent intrinsic mitochondrial pathway. Furthermore, HEFPs increased the level of reactive oxygen species (ROS) in HCT-116 and DLD1 cells. The addition of the antioxidant N-acetyl-L-cysteine reduced the ability of HEFPs to trigger the intrinsic mitochondrial pathway, indicating the role of ROS generation in the upstream pathway of HEFP-induced apoptosis. Therefore, the results described in this study could be of interest for further studies in finding functional foods or alternative therapeutic agents against colorectal cancer.

Colorectal carcinoma (CRC) is an aggressive malignancy with very limited therapeutic options. As a result, both morbidity and mortality of this malignancy are very high. It is well-established that Nostoc commune Vaucher is a type of healthy food and has been used as a traditional medicine against human cancers. However, the underlying mechanism(s) by which Nostoc commune Vaucher inhibits CRC was never described. Here we reported that polysaccharides from Nostoc commune Vaucher are a potent inhibitor of CRC growth by activating macrophages. Specifically, we purified polysaccharides from Nostoc commune and two fractions of these polysaccharides are able to inhibit the proliferation and growth of five human CRC cell lines with divergent genetic backgrounds. Through activating NF-κB and AKT/JNK1/2 signaling pathways, one fraction of polysaccharides significantly activated macrophages, which was reflected by the enlarged size of macrophages, enhanced phagocytosis and expression of TNF-α and IL-1β. In summary, this study demonstrated that the polysaccharides from Nostoc commune Vaucher are a potent activator of macrophages, which subsequently contributes to the inhibition of CRC.

Ulcerative colitis (UC) is evolving into a global burden with a substantially increasing incidence in developing countries. It is characterized by inflammation confined to mucosa and is recognized as an intestinal barrier disease. The intestinal microbiota plays a crucial role in UC pathogenesis. N. commune has long been appreciated as a healthy food and supplement worldwide and polysaccharides account for 60%. Here, we examined the amelioration of N. commune polysaccharides against acute colitis in mice induced by DSS and assessed the mediating role of gut microbiota. An integrated analysis of microbiome, metabolomics, and transcriptomics fully elaborated it markedly enhanced intestinal mucosal barrier function, including: increasing the relative abundance of Akkermansia muciniphila, uncultured_bacterium_g__norank_f__Muribaculaceae, and unclassified_g__norank_f__norank_o__Clostridia_UCG-014; decreasing microbiota-derived phosphatidylcholines and thromboxane 2 levels mapped to arachidonic acid metabolism; improving mucin2 biosynthesis and secretion; enhancing ZO-1 and occludin expression; reducing neutrophil infiltration; regulating the level of colitis-related inflammatory cytokines; involving inflammation and immune function-associated signaling pathways. Further, the mediation effect of gut microbiota was evaluated by administering a cocktail of antibiotics. In conclusion, our results demonstrated that N. commune polysaccharides predominantly reinforced the gut microbiota-mediated intestinal mucosal barrier to confer protection against UC and exhibited dramatic prebiotic-like functions, providing an alternative or complementary treatment for UC.