Immunomodulation of exopolysaccharide produced by Lacticaseibacillus rhamnosus ZFM216 in cyclophosphamide-induced immunosuppressed mice by modulating gut microbiota

This study investigated the immunoregulatory activity of exopolysaccharides (EPS) produced by Lacticaseibacillus rhamnosus ZFM216 in immunosuppressed mice induced by cyclophosphamide (CTX). The results showed that EPS treatment effectively improved the body weight, immune organ index and splenic lymphocyte proliferation. EPS also mitigated the damage of immune organs, restored intestinal morphology, and regulated the levels of serum hemolysin and cytokines (e.g. TNF-α, INF-γ and IL-10). EPS promoted the release of NO, TNF-α, IL-1β, and IL-6 in RAW 264.7 cells, however, such effect was inhibited in the presence of inhibitors of TLR4 and MAPKs signaling pathways-related proteins, confirming that EPS achieved the immunomodulation by activating these two signaling pathways. Additionally, EPS, as a prebiotic, effectively improved the diversity of microbial communities, regulated the relative abundance of dominant microbial communities, restored CTX-induced gut microbiota dysbiosis, and promoted the production of short chain fatty acids (SCFAs) in the gut of mice. Thus, immunoregulatory effect of EPS could be attributed to its good ability to modulate the gut microbiota. EPS produced by L. rhamnosus ZFM216 has promising application as an ingredient of functional foods due to its potent probiotic effect.