School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, China.
College of Clinical Medicine, Ningxia Medical University, Yinchuan, China.
PLoS One. 2023 Mar 13;18(3):e0277155. doi: 10.1371/journal.pone.0277155. eCollection 2023.
Based on the relationship between the gut microbiota and colorectal cancer, we developed a new probiotic powder for treatment of colorectal cancer. Initially, we evaluated the effect of the probiotic powder on CRC using hematoxylin and eosin staining, and evaluated mouse survival rate and tumor size. We then investigated the effects of the probiotic powder on the gut microbiota, immune cells, and apoptotic proteins using 16S rDNA sequencing, flow cytometry, and western blot, respectively. The results showed that the probiotic powder improved the intestinal barrier integrity, survival rate, and reduced tumor size in CRC mice. This effect was associated with changes in the gut microbiota. Specifically, the probiotic powder increased the abundance of Bifidobacterium animalis and reduced the abundance of Clostridium cocleatum. In addition, the probiotic powder resulted in decreased numbers of CD4+ Foxp3+ Treg cells, increased numbers of IFN-γ+ CD8+ T cells and CD4+ IL-4+ Th2 cells, decreased expression of the TIGIT in CD4+ IL-4+ Th2 cells, and increased numbers of CD19+ GL-7+ B cells. Furthermore, the expression of the pro-apoptotic protein BAX was significantly increased in tumor tissues in response to the probiotic powder. In summary, the probiotic powder ameliorated CRC by regulating the gut microbiota, reducing Treg cell abundance, promoting the number of IFN-γ+ CD8+ T cells, increasing Th2 cell abundance, inhibiting the expression of TIGIT in Th2 cells, and increasing B cell abundance in the immune microenvironment of CRC, thereby increasing the expression of BAX in CRC.
基于肠道微生物群与结直肠癌的关系,我们开发了一种新的益生菌粉来治疗结直肠癌。最初,我们使用苏木精和伊红染色来评估益生菌粉对 CRC 的影响,并评估小鼠的存活率和肿瘤大小。然后,我们使用 16S rDNA 测序、流式细胞术和 Western blot 分别研究了益生菌粉对肠道微生物群、免疫细胞和凋亡蛋白的影响。结果表明,益生菌粉改善了 CRC 小鼠的肠道屏障完整性、存活率,并降低了肿瘤大小。这种作用与肠道微生物群的变化有关。具体而言,益生菌粉增加了双歧杆菌属的丰度,降低了梭菌属 cocleatum 的丰度。此外,益生菌粉导致 CD4+Foxp3+Treg 细胞数量减少,IFN-γ+CD8+T 细胞和 CD4+IL-4+Th2 细胞数量增加,CD4+IL-4+Th2 细胞中 TIGIT 的表达减少,CD19+GL-7+B 细胞数量增加。此外,肿瘤组织中促凋亡蛋白 BAX 的表达也因益生菌粉而显著增加。总之,益生菌粉通过调节肠道微生物群、减少 Treg 细胞丰度、促进 IFN-γ+CD8+T 细胞数量增加、增加 Th2 细胞丰度、抑制 Th2 细胞中 TIGIT 的表达、增加 CRC 免疫微环境中 B 细胞的丰度,从而增加 CRC 中 BAX 的表达,改善了 CRC。