Central Laboratory, First Affiliated Hospital, Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, 116021, China.
Pharmacy Department, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, China.
J Nanobiotechnology. 2024 May 12;22(1):241. doi: 10.1186/s12951-024-02506-4.
Colorectal cancer (CRC) incidence is increasing in recent years due to intestinal flora imbalance, making oral probiotics a hotspot for research. However, numerous studies related to intestinal flora regulation ignore its internal mechanisms without in-depth research.
Here, we developed a probiotic microgel delivery system (L.r@(SA-CS)) through the layer-by-layer encapsulation technology of alginate (SA) and chitosan (CS) to improve gut microbiota dysbiosis and enhance anti-tumor therapeutic effect. Short chain fatty acids (SCFAs) produced by L.r have direct anti-tumor effects. Additionally, it reduces harmful bacteria such as Proteobacteria and Fusobacteriota, and through bacteria mutualophy increases beneficial bacteria such as Bacteroidota and Firmicutes which produce butyric acid. By binding to the G protein-coupled receptor 109A (GPR109A) on the surface of colonic epithelial cells, butyric acid can induce apoptosis in abnormal cells. Due to the low expression of GPR109A in colon cancer cells, MK-6892 (MK) can be used to stimulate GPR109A. With increased production of butyrate, activated GPR109A is able to bind more butyrate, which further promotes apoptosis of cancer cells and triggers an antitumor response.
It appears that the oral administration of L.r@(SA-CS) microgels may provide a treatment option for CRC by modifying the gut microbiota.
近年来，由于肠道菌群失衡，结直肠癌（CRC）的发病率不断上升，口服益生菌成为研究热点。然而，许多与肠道菌群调节相关的研究忽略了其内在机制，没有进行深入研究。
在这里，我们通过海藻酸钠（SA）和壳聚糖（CS）的层层包裹技术开发了一种益生菌微凝胶递送系统（L.r@（SA-CS）），以改善肠道微生物失调并增强抗肿瘤治疗效果。L.r 产生的短链脂肪酸（SCFAs）具有直接的抗肿瘤作用。此外，它减少了变形菌门和梭杆菌门等有害细菌，并通过细菌共生增加了产生丁酸的拟杆菌门和厚壁菌门等有益细菌。丁酸通过与结肠上皮细胞表面的 G 蛋白偶联受体 109A（GPR109A）结合，可以诱导异常细胞凋亡。由于结肠癌细胞中 GPR109A 的表达较低，MK-6892（MK）可用于刺激 GPR109A。随着丁酸盐产量的增加，激活的 GPR109A 能够结合更多的丁酸盐，这进一步促进了癌细胞的凋亡，并引发了抗肿瘤反应。
口服 L.r@（SA-CS）微凝胶可能通过改变肠道微生物群为 CRC 提供一种治疗选择。
