Exopolysaccharides from Genistein-Stimulated <i>Monascus purpureus</i> Ameliorate Cyclophosphamide-Induced Intestinal Injury via PI3K/AKT-MAPKs/NF-κB Pathways and Regulation of Gut Microbiota

Abstract

Exopolysaccharides from genistein-stimulated <i>Monascus purpureus</i> (G-EMP) exhibited immunomodulatory potential in vitro, but whether it had immune-enhancing effects in vivo and its potential mechanism are not yet known. Here, the immunomodulatory effects of G-EMP were investigated by establishing an immunosuppressed mouse model treated with cyclophosphamide (Cy). The results suggested that G-EMP effectively alleviated the signs of weight reduction and diet reduction caused by Cy, increased fecal water content and splenic index, and decreased the oxidative stress of the liver. Simultaneously, G-EMP improved Cy-induced intestinal injury by restoring villus length, increasing the number of cupped cells, upregulating the expression of mucin and tight junction proteins, and downregulating the ratio of apoptotic proteins (Bax/Bcl-2). It also boosted the levels of mouse colonic cytokines, CD4⁺ and CD8⁺ T cells. Additionally, G-EMP markedly enhanced immunomodulation via the activation of PI3K/AKT-MAPKs/NF-κB signal pathways. Furthermore, G-EMP intervention displayed a positive association with most immunological indexes by elevating the levels of short-chain fatty acids, varying gut microbiota composition, and enhancing beneficial bacteria (<i>Lactobacillaceae</i>, <i>Prevotellaceae,</i> and <i>S24-7</i>). These findings demonstrated that G-EMP can strengthen immunity, repair intestinal mucosal damage, regulate gut microbiota, and be a potential source of prebiotics.