Sulfated Alfalfa Polysaccharides Enhance Post‐Obesity Recovery Through Modulation of Gut Microbiota and Antioxidant Activity

Alfalfa polysaccharides (APs) and sulfated alfalfa polysaccharides (SAPs) have both demonstrated efficacy in mitigating obesity. This study was designed to explore the physiological modifications and the mechanisms underlying these changes in obese mice treated with APs and SAPs following a dietary transition. Obese mice underwent treatment with orlistat, APs, and SAPs for 2 months, after which the treatments were discontinued, and their high-fat diet was substituted with a basal diet. Subsequent evaluations were conducted to assess various physiological changes. Our results indicated that dietary modification led to normalization of feed intake and serum triglyceride levels in mice treated with APs and SAPs. Compared to mice treated with orlistat and those that remained untreated, mice receiving APs and SAPs exhibited significantly improved liver antioxidant capacity and immune function. Moreover, treatment with Orlistat, APs, and SAPs resulted in a reduction in intestinal permeability, achieved by enhancing colonic short-chain fatty acid levels and upregulating the expression of tight junction proteins in the colon. Treatments induced significant alterations in the colonic microbial community of the mice, which was characterized by an increased relative abundance of Bifidobacteria and a decreased Firmicutes-to-Bacteroidetes (F/B) ratio across all treatment groups. The most significant decrease in the F/B ratio was observed in the mice treated with SAPs. Our study indicates that, treatments with APs and SAPs improved antioxidant capacity and immune function in obese mice following dietary changes. In addition, APs and SAPs induced long-lasting alterations in the structure of the gut microbial community, which favored rapid health improvement.