Positive effect of a novel protein from <i>Pleurotus eryngii</i> on improving colitis: exploring potential mechanisms from the perspective of intestinal metabolism

<i>Pleurotus eryngii</i> (<i>P. eryngii</i>) protein has demonstrated potential anti-inflammatory effects, but the specific mechanism has not been reported. Our research found that <i>P. eryngii</i> protein improved colitis in mice through various pathways, including reducing levels of inflammatory cytokines, promoting oxidative stress homeostasis, and enhancing immune response capacity. 16S rDNA sequencing showed that under the intervention of <i>P. eryngii</i> protein, the relative abundance of the microbiota (<i>Escherichia</i>, <i>Shigella</i>, and <i>Lachnoclostridium</i>) that induced colitis decreased. Metabolomics results showed that the metabolism of lipids and lipid-like molecules was active, with a decrease in the content of steroids (delta 8,14-sterol and DG (14 : 1 (9Z)/16 : 1 (9Z)/0 : 0)) and an increase in the content of terpenoids ((<i>Z</i>)-alpha-bergamotenoic acid, sterebin-D, and alpha-terpineol). Pathway analysis found that the <i>P. eryngii</i> protein activated the cholesterol metabolism pathway through the production of terpenoids, thus promoting the production of very low-density lipoprotein (VLDL) and bile acids, which regulated the level of IL-10 and intestinal homeostasis. Multi-omics joint analysis found that the production of steroid metabolites could be inhibited by <i>Flavonifractor</i> and <i>Sphingomonas</i>, while the growth of harmful bacteria <i>Enterococcus</i> and <i>Lachnoclostridium</i> was likely to be restrained by the terpenoid metabolites. Overall, this study has illustrated that the <i>P. eryngii</i> protein prevented the production of harmful bacteria and activated the cholesterol metabolism pathway to resist inflammatory reactions by regulating the metabolism of lipids and lipid-like molecules.