Effect of the β-glucan from Lentinus edodes on colitis-associated colorectal cancer and gut microbiota

Colorectal cancer is the third most common cancer in the world, and therapies with safety are in great need. In this study, the beta-glucan isolated from Lentinus edodes was successfully fractionated into three fractions with different weight-average molecular weight (M-w) by ultrasonic degradation and used for the treatment of colorectal cancer. In our findings, the beta-glucan was successfully degraded with the M-w decreased from 2.56 x 10(6) Da to 1.41 x 10(6) Da, exhibiting the triple helix structure without conformation disruption. The in vitro results indicate that beta-glucan fractions inhibited colon cancer cell proliferation, induced colon cancer cell apoptosis, and reduced inflammation. The in vivo results based on Azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model demonstrate that the lower-molecular weight beta-glucan fraction showed stronger anti-inflammatory and anti-colon cancer activities by reconstructing intestinal mucosal barrier, increasing short chain fatty acids (SCFAs) content, regulating metabolism of gut microbiota, and rebuilding the gut microbiota structure with the increased Bacteroides and the decreased Proteobacteria at the phylum level, as well as with the decreased Helicobacter and the increased Muribaculum at the genus level. These findings provide scientific basis for using the beta-glucan to regulate gut microbiota as an alternative strategy in the clinical treatment of colon cancer.