A Polysaccharide Isolated from Dictyophora indusiata Promotes Recovery from Antibiotic-Driven Intestinal Dysbiosis and Improves Gut Epithelial Barrier Function in a Mouse Model

Abstract

Despite the tremendous biological activity of polysaccharides from the mushroom <i>Dictyophora indusiata</i>, its role in the restoration of gut microbiota has not yet been explored. The present study aimed to investigate whether <i>D. indusiata</i> polysaccharide (DIP) could modulate the recovery of gut microbiota composition and intestinal barrier function after broad-spectrum antibiotic-driven dysbiosis. Alteration and restoration in the microbial communities were elucidated by the Illumina MiSeq platform. Colon histology, expression of tight-junction associated proteins, and serum/tissue endotoxin and cytokine levels were evaluated. Two-week daily oral administration of clindamycin and metronidazole resulted in reduced bacterial diversity and richness, and perturbed the microbial flora at various taxonomic levels (altered Firmicutes/Bacteroidetes ratio and increased relative abundance of harmful flora (Proteobacteria<i>, Enterococcus</i>, and <i>Bacteroides</i>)), whereas DIP administration reversed the dysbiosis and increased beneficial flora, including Lactobacillaceae (lactic acid-producing bacteria), and Ruminococaceae (butyrate-producing bacteria). In addition, it resulted in the reduction of endotoxemia (through lipopolysaccharides (LPSs)) and pro-inflammatory cytokine (tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and interleukin 1β (IL-1β)) levels, with the increased expression of tight-junction associated proteins (claudin-1, occludin, and zonula occludens-1). These findings not only suggested a comprehensive understanding of the protective effects of a DIP in the restoration of gut microbiota but also highlighted its role in the enhancement of gut barrier integrity, reduction of inflammation and lowering of endotoxin levels in mice.