State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, PR China.
State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, PR China; Jiangxi-OAI Joint Research Institute, Nanchang University, Nanchang 330047, PR China.
Pharmacol Res. 2022 Oct;184:106406. doi: 10.1016/j.phrs.2022.106406. Epub 2022 Aug 18.
The gut microbiota plays a role in tumor therapy by participating in immune regulation. Here, we demonstrated through 8-day probiotic supplementation experiments and fecal microbiota transplantation experiments that Bifidobacterium animalis subsp. lactis SF enhanced the antitumor effect of irinotecan and prevented the occurrence of intestinal damage by modulating the gut microbiota and reducing the relative abundance of pro-inflammatory microbiota. Therefore, the intestinal inflammation was inhibited, the TGF-β leakage was reduced, and the PI3K/AKT pathway activation was inhibited. Thus, the tumor apoptotic autophagy was finally promoted. Simultaneously, the reduction of TGF-β relieved the immunosuppression caused by CPT-11, promoted the differentiation of CD4 and CD8 T cells in tumor tissue, and consequently inhibited tumor growth and invasion. This study disclosed the mechanism of B. lactis SF assisting CPT-11 in antitumor activity and suggested that B. lactis SF plays a new role in anticancer effects as a nutritional intervention.
肠道微生物群通过参与免疫调节在肿瘤治疗中发挥作用。在这里,我们通过 8 天的益生菌补充实验和粪便微生物群移植实验证明,动物双歧杆菌亚种。 lactis SF 通过调节肠道微生物群和减少促炎微生物群的相对丰度来增强伊立替康的抗肿瘤作用并预防肠道损伤的发生。因此,抑制了肠道炎症,减少了 TGF-β 的渗漏,并抑制了 PI3K/AKT 通路的激活。因此,最终促进了肿瘤凋亡自噬。同时,TGF-β 的减少缓解了 CPT-11 引起的免疫抑制,促进了肿瘤组织中 CD4 和 CD8 T 细胞的分化,从而抑制了肿瘤的生长和侵袭。这项研究揭示了 B. lactis SF 辅助 CPT-11 发挥抗肿瘤活性的机制,并表明 B. lactis SF 作为一种营养干预在抗癌作用中发挥新的作用。