需要探索联合疗法，通过食品益生菌提高结直肠癌免疫治疗的疗效。在本研究中，成功​​分离了源自鼠李糖乳杆菌GG（LGG-EV）的细胞外囊泡（EV）。将培养温度调整至 30°C 导致 LGG-EV 产量升高，并且青霉素的添加导致粒径减小。此外，LGG-EV在体内和体外Ca2环境下均具有更好的胃肠道稳定性。口服 LGG-EV 可以协同提高抗 PD-1 免疫疗法对结直肠癌的疗效。从机制上讲，LGG-EV通过增加肠系膜淋巴结中的CD8 T/CD4 T细胞比率以及提高肿瘤组织中MHC II DC细胞、CD4 T细胞和CD8 T细胞的比率来调节肠道免疫。与此同时，联合治疗小鼠的肠道微生物群多样性和有益细菌（如乳酸菌）的丰度有所增加。此外，与微生物群和抗肿瘤作用相关的血清代谢物水平也发生了显着变化，其中包括尿苷，抗PD-1和LGG-EV联合治疗使尿苷水平升高。我们的研究结果为 LGG-EV 作为后生元与免疫检查点抑制剂联合用于癌症治疗的发展提供了理论和机制见解。

There is a need to explore combination therapy to improve the efficacy of immunotherapy for colorectal cancer through food probiotics. In this study, extracellular vesicles (EV) derived from Lactobacillus rhamnosus GG (LGG-EV) were successfully isolated. Adjusting the culture temperature to 30 °C led to an elevated LGG-EV yield, and the addition of penicillin resulted in a decrease in particle size. In addition, LGG-EV have better gastrointestinal tract stability in a Ca2+ environment in vivo and in vitro. Oral administration of LGG-EV synergistically improved anti-PD-1 immunotherapy efficacy against colorectal cancer. Mechanistically, LGG-EV modulated intestinal immunity by increasing the CD8+ T/CD4+ T cell ratio in mesenteric lymph nodes and enhancing the ratio of MHC II+ DC cells, CD4+ T cells, and CD8+ T cells in tumor tissues. Meanwhile, the diversity of the gut microbiota and the abundance of beneficial bacteria, such as Lactobacillus, increased in the combined-treatment mice. In addition, there were significant changes in the levels of serum metabolites associated with the microbiota and anti-tumor effects, including uridine, which was elevated by the combination of anti-PD-1 and LGG-EV treatment. Our findings provide theoretical and mechanistic insights into the development of LGG-EV as postbiotics in combination with immune checkpoint inhibitors for cancer therapy.