Crude Corbicula fluminea carbohydrate extract attenuates cyclophosphamide-induced immune and intestinal injury in mice in association with gut microbiota remodeling.

Corbicula fluminea has been increasingly recognized for its nutritional and therapeutic potential. Corbicula fluminea carbohydrate extract (CFPS) is one of the active components of Corbicula fluminea. In this study, two low-molecular-weight oligosaccharide fractions were isolated from crude CFPS for preliminary physicochemical characterization, and the immunomodulatory activity and gut regulatory activities of crude CFPS were investigated, respectively. The results showed that the yield of crude CFPS was 4.97%. Two purified fractions (CFPS-1 and CFPS-2) were obtained with molecular weights of 3.3 × 103 Da and 0.6 × 103 Da, respectively. CFPS-1 was composed of glucose (89.1%) and fucose (10.9%), while CFPS-2 contained mannose (10.8%), galactose (4.3%), galacturonic acid (0.7%), and glucose (84.2%). In immunosuppressed mice, crude CFPS administration was associated with ameliorated intestinal barrier damage, upregulated tight junction proteins (ZO-1, occludin, and claudins), and reduced levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-12), which correlated with downregulated TLR4/NF-κB pathway activation. Gut microbiota analysis revealed crude CFPS-associated shifts in microbial composition, including increased Firmicutes and decreased Bacteroidota. Pearson correlation analysis showed positive association between Firmicutes/Lactobacillus abundance and intestinal barrier proteins, and negative correlation with pro-inflammatory cytokines. These associative findings support further investigation of crude CFPS as a functional food candidate, though causal mechanisms remain to be established.