Ludangshen oral liquid ameliorates cyclophosphamide-induced immunosuppression in mice: Insights from metabolomic, gut microbiota, and multi-omics correlation analyses.

Abstract

Immune dysfunction elevates susceptibility to infections, diseases, and tumors. While conventional immunomodulators often cause adverse effects, plant-derived therapies offer superior stability and hold considerable research promise. Codonopsis pilosula (Franch.) Nannf., a traditional medicinal herb, replenishes blood, promotes fluid production, and tonifies qi. Ludangshen Oral Liquid (LDSOL), a preparation derived from C. pilosula, contains multiple bioactive constituents, including lobetyolin; however, its immunomodulatory effects and their associations with host metabolism and gut microbiota remain unclear. In this study, we investigated the effects of LDSOL in cyclophosphamide-induced immunosuppressed mice using pharmacodynamic evaluation, metabolomics, 16S rRNA sequencing, and multi-omics correlation analysis. Our results demonstrated that LDSOL alleviated hepatosplenomegaly and thymic atrophy, regulated blood cell counts, and elevated levels of IL-2, IL-6, TNF-α, IFN-γ, and IgG. It also restored the balance between Th17/Treg and Th1/Th2 subsets, suggesting improved immune responses. Metabolomic and 16S rRNA analyses revealed that LDSOL modulated endogenous metabolites (e.g., L-phenylalanine, serotonin) and gut bacterial communities (e.g., Lactobacillus, Ruminococcus). Integrated correlation analysis further identified potential associations among altered gut microbial taxa, LDSOL-responsive metabolites, and immune-related parameters. Collectively, these findings indicate that LDSOL ameliorates cyclophosphamide-induced immunosuppression in mice and suggest that metabolic remodeling and gut microbiota alterations may be associated with its immunomodulatory effects.