Department of Biochemistry and Molecular Biology, Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada.
Sci Rep. 2016 Nov 22;6:37627. doi: 10.1038/srep37627.
In type 1 diabetes, restoration of normoglycemia can be achieved if the autoimmune attack on beta cells ceases and insulin requirement is met by the residual beta cells. We hypothesize that an adjunctive therapy that reduces insulin demand by increasing insulin sensitivity will improve the efficacy of an immunotherapy in reversing diabetes. We tested the gut microbiota-modulating prebiotic, oligofructose (OFS), as the adjunctive therapy. We treated non-obese diabetic mice with an immunotherapy, monoclonal anti-CD3 antibody (aCD3), with or without concurrent dietary supplement of OFS. After 8 weeks of OFS supplement, the group that received both aCD3 and OFS (aCD3 + OFS) had a higher diabetes remission rate than the group that received aCD3 alone. The aCD3 + OFS group had higher insulin sensitivity accompanied by reduced lymphocytic infiltrate into the pancreatic islets, higher beta-cell proliferation rate, higher pancreatic insulin content, and secreted more insulin in response to glucose. The addition of OFS also caused a change in gut microbiota, with a higher level of Bifidobacterium and lower Clostridium leptum. Hence, our results suggest that OFS can potentially be an effective therapeutic adjunct in the treatment of type 1 diabetes by improving insulin sensitivity and beta-cell function, leading to improved glycemic control.
在 1 型糖尿病中，如果针对β细胞的自身免疫攻击停止并且剩余的β细胞满足胰岛素需求，则可以恢复正常血糖水平。我们假设，通过增加胰岛素敏感性来降低胰岛素需求的辅助治疗将提高免疫疗法逆转糖尿病的疗效。我们测试了肠道微生物群调节的益生元低聚果糖 (OFS) 作为辅助治疗。我们用抗 CD3 单克隆抗体 (aCD3) 对非肥胖型糖尿病小鼠进行免疫治疗，同时或不进行 OFS 的饮食补充。在 8 周的 OFS 补充后，同时接受 aCD3 和 OFS 治疗的组（aCD3+OFS）的糖尿病缓解率高于仅接受 aCD3 治疗的组。aCD3+OFS 组的胰岛素敏感性更高，胰岛内淋巴细胞浸润减少，β细胞增殖率更高，胰腺胰岛素含量更高，对葡萄糖的胰岛素分泌更多。OFS 的添加还导致肠道微生物群发生变化，双歧杆菌水平升高，而梭状芽胞杆菌属 leptum 水平降低。因此，我们的结果表明，OFS 通过改善胰岛素敏感性和β细胞功能，有可能成为治疗 1 型糖尿病的有效治疗辅助手段，从而改善血糖控制。
