Weiwei Ma Hang Sun Lian Lian Lidong GUO Yanyan Wang Lili Huang ^*

• Heilongjiang University of Chinese Medicine, Harbin, China

The increasing stress of modern life has led to a decline in immunity, sparking widespread interest in new strategies to boost immune function. Lactiplantibacillus plantarum and stachyose have gained attention for their immune-regulating effects, but the mechanisms of their combined application remain unclear. This study evaluated the immunomodulatory effects of Lactiplantibacillus plantarum CCFM8661 combined with stachyose in cyclophosphamide-induced immunocompromised mice. Mice were divided into the normal control group, model control group (normal saline), positive drug control group (levamisole hydrochloride, 10 mg/kg), and low, medium, and high-dose groups (1.5×105, 1.5×106, and 1.5×107 CFU of Lactiplantibacillus plantarum CCFM8661 + 1.5 mg stachyose). Each treatment group received continuous oral gavage administration for 28 days. On days 23 and 24, except for the normal control group, all other groups were intraperitoneally injected with cyclophosphamide (40 mg/kg) to establish an immunosuppressed model. On day 28, 30 minutes after the final administration, the mice were euthanized to collect the thymus, spleen, serum, ileum, and feces for subsequent analysis of immune indicators, intestinal barrier function, serum cytokines, and intestinal microbiota. The combination significantly improved immune organ atrophy, restored intestinal morphology, and normalized cytokine levels in immunosuppressed mice, indicating enhanced immune function. Additionally, it restored intestinal microbiota diversity by increasing the abundance of Muribaculaceae while reducing Lachnospiraceae, potentially promoting intestinal homeostasis. This study offers theoretical and pharmacological support for the combined use of Lactiplantibacillus plantarum CCFM8661 and stachyose as a novel preparation for immunomodulation.