[Poria cocos polysaccharide alleviates cyclophosphamide-induced intestinal barrier dysfunction and inflammation in...

To investigate the protective effects of Poria cocos polysaccharide (PCP) against cyclophosphamide (CTX)-induced intestinal mucosal injury and its impact on gut flora and their metabolites in mice.

Adult BALB/C mice were randomized into normal control group, CTX model group, glutamine (positive control) group, and low-, medium- and high-dose PCP treatment groups. In all but the normal control group, the mice were subjected to modeling of CTX-induced intestinal mucosal injury by intraperitoneal CTX injections for 3 days, followed by treatment with gavage of normal saline, glutamine (300 mg/kg), or PCP at 75, 150, or 300 mg/kg for 7 consecutive days. The colonic expressions of tight junction proteins (occludin and ZO-1), serum endotoxin, D-lactate, and DAO levels, intestinal permeability, colon injury, and colonic cytokine levels (IL-4, IL-22, IL-17A, and IFN-γ mRNA) were assessed. Gut microbiota, short-chain fatty acids (SCFAs; mainly acetates and propionates) and colonic GPR41 expression were analyzed using 16S rRNA sequencing, GC-MS, and Western blotting, respectively. Fecal microbiota transplantation (FMT) experiment was conducted to validate the role of gut microbes in PCP-mediated repair of intestinal injuries.

Compared with those in the model group, the mice treated with PCP showed significantly increased colonic occludin and ZO-1 expressions, reduced serum endotoxin, D-lactate and DAO levels, and lowered intestinal permeability with increased colonic expressions of IL-4, IL-22, IL-17A, and IFN-γ mRNA. PCP treatment obviously increased the abundance of Muribaculaceae, decreased Lactobacillus and Bacteroides, increased the contents of acetate and propionate in the colon, and upregulated colonic GPR41 expression. The results of FMT experiment confirmed the crucial role of gut microbes in PCP-mediated repair of CTX-induced intestinal injuries in mice.

PCP can protect against CTX-induced intestinal mucosal injury in mice possibly by modulating gut flora and SCFAs metabolism to enhance intestinal defense capacity.