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This study explored the immunomodulatory effects of a prebiotic formula consisting of 2'-fucosyllactose (2'-FL), galacto-oligosaccharides (GOSs), and fructo-oligosaccharides (FOSs) (hereinafter referred to as 2FGF) in cyclophosphamide (CTX)-induced immunosuppressed BALB/c mice and its underlying mechanisms. Sixty healthy female BALB/c mice were randomly divided into the following groups: normal control (NC) group; CTX treatment (CTX) group; 2FGF low-dose (2FGF-L) group; 2FGF medium-dose (2FGF-M) group; and 2FGF high-dose (2FGF-H) group. An immunosuppressed model was established in the 2FGF-H group by intraperitoneal injection of 80 mg/kg CTX. After 30 days of 2FGF intervention, peripheral blood, spleen tissue, thymus tissue, and intestinal tissue from the mice were collected and analyzed. The changes in weight and food intake of the mice were recorded weekly. Hematoxylin-eosin (HE) staining was used to observe the histological change of the spleen tissue. Enzyme-linked immunosorbent assay (ELISA) was employed to detect cytokine levels in peripheral blood. Flow cytometry was used to analyze T lymphocyte subgroup ratio of splenic lymphocytes. Western blot analysis was conducted on intestinal tissues to assess the expression of proteins involved in the tight junction, toll-like receptor 4 (TLR4), mitogen-activated protein kinase (MAPK), and nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) signaling pathways. Additionally, molecular techniques were used to analyze the intestinal microbiota. The results showed that 2FGF restored CTX-induced splenic injury, increased the number of splenic T lymphocytes, and elevated serum cytokines such as interleukin-4 (IL-4) and IL-10. In the intestine, 2FGF upregulated the expression of intestinal epithelial tight junction proteins such as Claudin-1 and zonula occludens 1 (ZO-1), thereby enhancing intestinal barrier function and activating the MAPK and NF-κB pathways via TLR4. Furthermore, 2FGF elevated the α-diversity (Shannon and Simpson indices) of the gut microbiota in CTX-induced immunosuppressed mice, enriching bacteria species positively correlated with anti-inflammatory cytokines (e.g., IL-4) such as and and negatively correlated with pro-inflammatory cytokines (e.g., IL-1β) such as . The results suggest that 2FGF may enhance immunity via the gut-immune axis. The 2FGF prebiotic formula showed an immunomodulatory effect in CTX-induced immunosuppressed mice, and the mechanism of which might involve optimizing the gut flora, enhancing intestinal homeostasis, strengthening the intestinal barrier, and promoting the expression of immune factors by regulating the TLR-4/MAPK/NF-κB pathway.

本研究探讨了由 2'-岩藻糖基乳糖（2'-FL）、半乳糖寡糖（GOS）和果寡糖（FOS）组成的一种益生元配方（以下简称 2FGF）对环磷酰胺（CTX）诱导的免疫抑制 BALB/c 小鼠的免疫调节作用及其机制。

将 60 只健康雌性 BALB/c 小鼠随机分为以下几组：正常对照组（NC）；CTX 处理组（CTX）；2FGF 低剂量组（2FGF-L）；2FGF 中剂量组（2FGF-M）；2FGF 高剂量组（2FGF-H）。2FGF-H 组通过腹腔注射 80mg/kgCTX 建立免疫抑制模型。2FGF 干预 30 天后，采集小鼠外周血、脾组织、胸腺组织和肠道组织进行分析。每周记录小鼠的体重和采食量变化。采用苏木精-伊红（HE）染色观察脾组织的组织学变化。采用酶联免疫吸附试验（ELISA）检测外周血细胞因子水平。采用流式细胞术分析脾淋巴细胞 T 淋巴细胞亚群比例。采用 Western blot 分析肠道组织中紧密连接、Toll 样受体 4（TLR4）、丝裂原活化蛋白激酶（MAPK）和核因子 kappa-轻链增强子的 B 细胞（NF-κB）信号通路相关蛋白的表达。此外，采用分子技术分析肠道微生物群。

结果表明，2FGF 恢复了 CTX 诱导的脾损伤，增加了脾 T 淋巴细胞数量，并提高了血清细胞因子如白细胞介素-4（IL-4）和白细胞介素-10（IL-10）水平。在肠道中，2FGF 上调了 Claudin-1 和 zonula occludens 1（ZO-1）等肠道上皮紧密连接蛋白的表达，从而增强了肠道屏障功能，并通过 TLR4 激活 MAPK 和 NF-κB 通路。此外，2FGF 提高了 CTX 诱导免疫抑制小鼠肠道微生物群的 α 多样性（Shannon 和 Simpson 指数），增加了与抗炎细胞因子（如 IL-4）呈正相关的细菌种类，并减少了与促炎细胞因子（如 IL-1β）呈负相关的细菌种类。

结果表明，2FGF 可能通过肠道免疫轴增强免疫力。2FGF 益生元配方对 CTX 诱导的免疫抑制小鼠具有免疫调节作用，其机制可能涉及通过调节 TLR-4/MAPK/NF-κB 通路优化肠道菌群，增强肠道稳态，加强肠道屏障，并促进免疫因子的表达。