Immune regulation mechanism mediated by Glycyrrhiza polysaccharide

Abstract Background Cancer, rheumatic heart disease, gastrointestinal disease, and arthritis are associated with immune system disorders. Low-molecular-weight Glycyrrhiza polysaccharide (GP1) can improve immune disorders and intestinal mucosal injury by regulating gut microbiota; however, its immune regulation mechanism remains unclear. Herein, based on the structural analysis of GP1, we aimed to reveal its degradation route and immune regulation mechanism. Results GP1 mainly comprised glucose (98.59%) with (1→4)-α-D-Glcp, (1→4,6)-α-D-Glcp, and T-α-D-Glcp as the main backbone. GP1 was primarily degraded by gut microbiota in the colon and significantly increased the abundance of Muribaculum and Lactobacillus. Muribaculum_sp._H5 was the most important bacteria for degrading GP1, metabolized GP1 into D-glucose-1-phosphate by glycogen phosphorylase and produced the characteristic metabolites succinic acid, D-gluconic acid, D-galacturonic acid, and 4-pyridoxic acid, which was the first discovered to regulate immunity. These metabolites and probiotics produced from GP1 exerted an immunoregulatory effect together. Conclusions Our results demonstrate the prebiotic potential of GP1 as a natural and non-toxic regulator for improving the structure of gut microbiota and alleviating immune disorders, which may be a new strategy to alleviate the side effects of tumor treatment.