Alleviative Effect of Stropharia rugosoannulata Exopolysaccharide on d ‐Galactose‐Induced Gut Inflammation and Oxidative Stress by Modulating Gut Microbiota

The exopolysaccharide SREP‐1, purified from the fermentation broth of Stropharia rugosoannulata , exhibited antiaging potential. As aging significantly alters gut structure and function, protective effect of SREP‐1 was investigated using a d ‐galactose‐induced aging mouse model. SREP‐1 administration reversed D‐galactose‐induced body weight loss and colon damage, as evidenced by improved histopathology. SREP‐1 mitigated weight loss and colon damage, enhanced the activities of antioxidants (SOD, GSH‐Px, and CAT), and reduced the level of MDA. It decreased proinflammatory cytokines (TNF‐α, IL‐1β, and IL‐6) and elevated IL‐10 in colon tissue, while boosting serum immunoglobulins (IgG and IgM). Crucially, these effects were abolished by antibiotic pretreatment, highlighting the role of gut microbiota in SREP‐1 bioactivity. This role was further confirmed through fecal microbiota transplantation (FMT) and fecal supernatant transplantation (FST) experiments. Based on 16S rRNA sequencing, SREP‐1 restored gut microbial diversity, increased beneficial genera (e.g., Faecalibacterium , Akkermansia , Lactobacillus , and Bacteroides ), and decreased harmful bacteria (e.g., Escherichia‐Shigella and Collinsella ). Furthermore, short‐chain fatty acids (SCFAs) levels were elevated in the SREP‐1 group, which might regulate GPCRs/NF‐κB/Nrf2 signaling pathways and exert biological activity. This study revealed the potential of SREP‐1 to alleviate aging‐related intestinal dysfunction and underscored the crucial role of gut microbiota in mediating these effects.