Polysaccharide A1 from bran-fried Atractylodes lancea enhances mucosal immunity via Faecalibaculum rodentium-mediated B-cell class-switch DNA recombination

ABSTRACT Chemotherapy-induced intestinal injury is a common adverse effect during tumor chemotherapy, which seriously impairs patients’ quality of life and may even lead to treatment interruption. Natural polysaccharides have been proven to alleviate intestinal damage by regulating the gut microbiota. As a dietary supplement, polysaccharide A1 from bran-fried Atractylodes lancea (FALP-A1) exhibits notable immunoregulatory and intestinal protective effects. However, the specific mechanisms underlying their modulation of gut microbiota and enhancement of intestinal mucosal immunity remain unclear. In this study, a chemotherapy-induced intestinal injury mouse model demonstrated that FALP-A1 significantly increased body weight, organ index, and blood cell count, upregulated the expression of intestinal tight junction proteins zona occludens-1 (ZO-1) and occludin, and repaired intestinal barrier function. Moreover, FALP-A1 elevated the number of IgA + B cells and the level of secreted immunoglobulin A (sIgA), thereby enhancing intestinal mucosal immunity. FALP-A1 also reversed gut microbiota dysbiosis and the decrease in short-chain fatty acids (SCFAs) levels in treated mice, significantly enriching the SCFAs-producing probiotic Faecalibaculum rodentium ( F. rodentium ). The pseudo-sterile animal model and fecal microbiota transplantation experiments further confirmed that the protective effects of FALP-A1 on intestinal injury and mucosal immunity are dependent on the gut microbiota. Notably, transplantation of F. rodentium significantly improved pathological symptoms and enhanced mucosal immunity in chemotherapy-induced intestinal injury mice, further verifying the important role of this strain. Importantly, this study reveals that FALP-A1 promotes B-cell class switch DNA recombination (CSR) by upregulating the F. rodentium /SCFAs/activation-induced cytidine deaminase (AICDA)-sIgA axis, thereby potentiating intestinal mucosal immune responses. These findings provide a new perspective on the mechanisms by which natural polysaccharides alleviate intestinal injury and enhance mucosal immunity, and offer potential strategies for the clinical prevention and treatment of chemotherapy-induced intestinal injury.