Low weight polysaccharide of Hericium erinaceus ameliorates ulcerative colitis in C57BL/6 mice by inhibiting the NLRP3 inflammasome activation in association with gut microbiota modulation

Ulcerative colitis (UC) is one of the typical inflammatory bowel diseases caused by dysregulated immunity, which still requires novel therapeutic medicine with high efficacy and low toxicity. Hericium erinaceus has been widely used to treat different health problems especially gastrointestinal sickness in China for thousands of years. Here, we isolated, purified and characterized a novel low weight polysaccharide (HEP10, Mw: 9.9 kDa) from the mycelia of H. erinaceus in submerged culture. We explored the therapeutic effect of HEP10 on UC and explored its underlying mechanisms. HEP10 suppressed the production of TNF, IL-1, IL-6, inducible iNOS and COX-2, in LPS challaged murine macrophage RAW264.7 cells, as well as in colon from DSS-induced colitis mice. Moreover, HEP10 treatment markedly suppressed the activation of NLRP3 inflammasome, NF-KAPPA B, AKT and MAPK pathways in vitro and in vivo. In order to study whether HEP10 could regulate gut microbiota, caecel DNA was extracted and analyzed by 16S rDNA high-throughput sequencing. The results showed that HEP10 reversed DSS-induced alternation of the gut community composition and structure by decreasing the relative abundances of genus Aeromicrobium and Cellvibrio, while increasing Akkermansia muciniphila and also promote functional shifts in gut microbiota. In conclusion, HEP10 ameliorates DSS-induced intestinal injury in mice, which suggests that HEP10 can serve as a protective dietary component against ulcerative colitis.