Abstract: Objective: To investigate the protective effect of fermented Lycium barbarum polysaccharides (FLBP) on the intestine in an aging mouse model. Methods: The aging model was established by continuous subcutaneous injection of 1 000 mg/(kg mb · d) D-galactose in the back of the neck, followed by gavage of low (150 mg/(kg mb · d)) and high (300 mg/(kg mb · d)) doses of FLBP. After 10 weeks, body mass, organ indexes, serum inflammatory markers and anti-inflammatory indicators including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and IL-10 levels, intestinal permeability, intestinal barrier damage biomarkers such as lipopolysaccharide (LPS) and lipopolysaccharide binding protein (LBP) contents, the histological structure of the colon, colonic mucin 2 (Muc2) expression, intestinal flora composition and fecal short-chain fatty acid contents were detected and analyzed. Results: High-dose FLBP antagonized D-galactose-induced growth retardation and thymus atrophy, decreased the serum levels of TNF-α, IL-1β and IL-6 and significantly increased serum IL-10 levels in the aging mice (P < 0.05). Furthermore, FLBP significantly ameliorated colonic barrier damage in mice, as evidenced by a significant decrease in intestinal permeability, LPS and LBP contents (P < 0.05), alterations in colonic tissue structure, and a significant increase in MUC2 secretion (P < 0.05). Meanwhile, FLBP regulated the gut microbiota composition by changing the α- and β-diversity, increasing the relative abundance of the beneficial bacteria norank_f_Muribaculaceae and Lactobacillus, and decreasing the relative abundance of the harmful bacteria Atopostipes and Jeotgalicoccus, and increasing the fecal contents of acetic acid, propionic acid, valeric acid and isobutyric acid significantly (P < 0.05). Conclusion: High-dose FLBP reduced circulating pro-inflammatory cytokine levels and enhanced anti-inflammatory function in aging mice, which might be related to improving colonic barrier function, regulating the intestinal flora composition, and increasing the levels of beneficial SCFAs in the intestinal tract of mice. This study provides a theoretical reference for the application of FLBP as a functional food ingredient for intestinal health.

Key words: Lycium barbarum polysaccharides; aging; intestinal flora; fermentation; short-chain fatty acids