Research and Development Department, Glac Biotech Co., Ltd, Tainan, Taiwan.
Department of Pediatrics, National Cheng Kung University Hospital, Tainan, Taiwan.
BMJ Open Diabetes Res Care. 2020 Apr;8(1). doi: 10.1136/bmjdrc-2019-001028.
Patients with type 2 diabetes mellitus (T2DM) exhibit strong insulin resistance or abnormal insulin production. Probiotics, which are beneficial live micro-organisms residing naturally in the intestinal tract, play indispensable roles in the regulation of host metabolism. However, the detailed mechanisms remain unclear. Here, we evaluate the mechanisms by which probiotic strains mediate glycemic regulation in the host. The findings should enable the development of a safe and natural treatment for patients with T2DM.
Sugar consumption by more than 20 strains of species was first evaluated. The probiotic strains that exhibited high efficiency of sugar consumption were further coincubated with Caco-2 cells to evaluate the regulation of sugar absorption in gut epithelial cells. Finally, potential probiotic strains were selected and introduced into a T2DM animal model to study their therapeutic efficacy.
Among the tested strains, AP-32 and GL-104 had higher monosaccharide consumption rates and regulated the expression of monosaccharide transporters. Glucose transporter type-5 and Na-coupled glucose transporter mRNAs were downregulated in Caco-2 cells after AP-32 and GL-104 treatment, resulting in the modulation of intestinal hexose uptake. Animal studies revealed that diabetic mice treated with AP-32, GL-104, or both showed significantly decreased fasting blood glucose levels, improved glucose tolerance and blood lipid profiles, and attenuated diabetes-mediated liver and kidney injury.
Our data elucidate a novel role for probiotics in glycemic regulation in the host. AP-32 and GL-104 directly reduce monosaccharide transporter expression in gut cells and have potential as therapeutic probiotics for patients with T2DM.
2 型糖尿病（T2DM）患者表现出强烈的胰岛素抵抗或胰岛素产生异常。益生菌是一种有益的、天然存在于肠道内的活菌，在调节宿主代谢方面发挥着不可或缺的作用。然而，其详细机制尚不清楚。在这里，我们评估了益生菌菌株调节宿主血糖的机制。这些发现应该能够为 T2DM 患者开发出安全和自然的治疗方法。
首先评估了超过 20 株 种的菌株对糖的消耗能力。然后将具有高效糖消耗能力的益生菌菌株与 Caco-2 细胞共孵育，以评估其对肠道上皮细胞糖吸收的调节作用。最后，选择潜在的益生菌菌株并引入 T2DM 动物模型，以研究其治疗效果。
在测试的菌株中，AP-32 和 GL-104 具有更高的单糖消耗率，并调节单糖转运蛋白的表达。AP-32 和 GL-104 处理后，Caco-2 细胞中葡萄糖转运蛋白 5 和 Na 偶联葡萄糖转运体 mRNA 下调，导致肠道己糖摄取的调节。动物研究表明，用 AP-32、GL-104 或两者联合治疗的糖尿病小鼠空腹血糖水平显著降低，葡萄糖耐量和血脂谱得到改善，糖尿病介导的肝肾功能损伤得到减轻。
我们的数据阐明了益生菌在宿主血糖调节中的新作用。AP-32 和 GL-104 直接降低肠道细胞中的单糖转运蛋白表达，具有作为 T2DM 治疗益生菌的潜力。
