Milk-processed Polygonatum cyrtonema Hua ameliorates cyclophosphamide-induced immunosuppression in mice by regulating...

Immune dysfunction is linked to the progression of various diseases. Milk-processed Polygonatum cyrtonema Hua (MPC) is a traditional medicine with nourishing effects in the Qinghai-Tibet Plateau region of China. However, the immune-enhancing effect of MPC and its underlying mechanism remain unclear.

This study aims to investigate the therapeutic effect and underlying mechanism of MPC on immunosuppressed mice.

A cyclophosphamide (CY)-induced immunosuppressive mouse model was established to evaluate the effects of MPC on the gut microbiota, intestinal barrier and immune response.

The chemical composition of MPC was identified by UPLC-Q-Exactive Orbitrap MS technology. Immune organ weight, body weight, colon length, biochemical parameters, and histopathology were examined. The levels of three short-chain fatty acids (SCFAs) were quantified via HPLC. 16S rRNA sequencing, fecal microbiota transplantation (FMT), antibiotic intervention, and Western blot were applied to explore the mechanism of MPC.

MPC significantly enhanced the production of some key cytokines (IL-2, IFN-γ, IL-4, IL-10, and TGF-β3), immunoglobulins (IgM and IgG), and transcription factors (T-bet, GATA-3, RORγt, and Foxp3). Additionally, MPC maintained intestinal mucosal integrity by upregulating tight junction proteins ZO-1, Claudin-1, E-cadherin, and Occludin. 16S rRNA sequencing of fecal samples revealed that MPC increased the relative abundance of beneficial SCFA-producing bacteria, specifically Lachnospiraceae_UCG-006, while decreasing the relative abundance of several pathogenic taxa, including Prevotellaceae, Alloprevotella, and Eubacterium_coprostanoligenes_group. Notably, antibiotic intervention and FMT experiments demonstrated that the immune-enhancing effect of MPC was dependent on the gut microbiota. MPC also increased the levels of three SCFAs including acetate, propionate, and butyrate. Besides, MPC was found to activate the SCFAs/GPR43/Blimp-1 pathway, leading to the production of IL-10, which enhanced the immune response.

This study demonstrates for the first time that MPC has a significant immune-enhancing effect. The mechanisms include restoring the balance of gut microbiota, promoting the production of SCFAs, repairing intestinal mucosal damage and enhancing immune function. These findings support the potential of MPC as a natural agent for improving gut health and systemic immunity.