Zhang Chao, Zhang Qi, Zhang Xiaoxu, Du Shuang, Zhang Yong, Wang Xifan, Liu Yinghua, Fang Bing, Chen Juan, Liu Rong, Hao Yanling, Li Yixuan, Wang Pengjie, Zhao Liang, Feng Haihong, Zhu Longjiao, Chen Lishui, Chen Shuxing, Wang Fuqing, Jiang Zhengqiang, Ji Yuting, Xiao Ran, Wang Ran, He Jingjing
Department of Nutrition and Health, Key Laboratory of Functional Dairy, Co-constructed by Ministry of Education and Beijing Government, China Agricultural University, Beijing 100193, China.
Mengniu Hi-Tech Dairy Product Beijing Co., Ltd., Beijing 101100, China.
Clin Nutr. 2025 Jan;44:248-258. doi: 10.1016/j.clnu.2024.11.042. Epub 2024 Dec 5.
Combining probiotics and prebiotics in synbiotics may present a synergistic approach to improve type 2 diabetes mellitus (T2DM); however, further evidence is required to establish the comparative efficacy of synbiotics versus probiotics. This study aimed to evaluate the effects of Bifidobacterium animalis subsp. lactis MN-Gup (MN-Gup) and a synbiotic mixture of MN-Gup and galactooligosaccharide (MN-Gup-GOS) on glycemic control in T2DM patients and explore possible mechanisms.
This randomized, double-blind, placebo-controlled clinical trial assigned 120 T2DM patients, to receive MN-Gup, MN-Gup-GOS, or placebo intervention for 12 weeks. The primary outcome was fasting blood glucose (FBG), with secondary outcomes including hemoglobin A1C (HbA1C), insulin, homeostatic model assessment of insulin resistance (HOMA-IR), inflammatory indicators, oxidative stress indicators, gastrointestinal hormones, gut microbiota, and bile acids (BAs).
The median age of the 120 participants was 59 years (interquartile range: 55-62 years), with 40 being men. Compared to baseline, all three groups exhibited significant reductions in FBG. Additionally, the MN-Gup-GOS group demonstrated significant decreases in HbA1c, serum insulin, and HOMA-IR after intervention, whereas no such reductions were observed in the placebo and MN-Gup groups. Regarding the between-group comparisons, the MN-Gup-GOS intervention showed a significantly greater reduction in FBG compared to the placebo (least squares mean difference [95 % CI], -0.69 [-1.29, -0.10] mmol/L, P = 0.022) and MN-Gup (-0.59 [-1.17, -0.01], P = 0.047) group, but not for other indicators of glucose metabolism. Additionally, MN-Gup and MN-Gup-GOS intervention, especially the latter, significantly modified inflammation, oxidative stress, gut microbiota, serum BAs, and GLP-1 levels. Correlation analysis showed significant associations between changes in certain gut microbiota (Bifidobacterium) and BAs (deoxycholic acid and lithocholic acid) with glycemic indicators.
The auxiliary effect of synbiotics MN-Gup-GOS on reducing FBG levels surpassed that of MN-Gup probiotics alone in T2DM patients, potentially attributed to the enhanced modulation of gut microbiota, BAs, and GLP-1 secretion.
This study was registered on the website of www.chictr.org.cn, number ChiCTR2100052187.
将益生菌和益生元组合成合生元可能是一种改善2型糖尿病（T2DM）的协同方法；然而，需要更多证据来确定合生元与益生菌相比的疗效。本研究旨在评估动物双歧杆菌乳亚种MN-Gup（MN-Gup）以及MN-Gup与低聚半乳糖的合生元混合物（MN-Gup-GOS）对T2DM患者血糖控制的影响，并探索可能的机制。
本随机、双盲、安慰剂对照临床试验纳入120例T2DM患者，接受MN-Gup、MN-Gup-GOS或安慰剂干预12周。主要结局为空腹血糖（FBG），次要结局包括糖化血红蛋白（HbA1C）、胰岛素、胰岛素抵抗稳态模型评估（HOMA-IR）、炎症指标、氧化应激指标、胃肠激素、肠道微生物群和胆汁酸（BAs）。
120名参与者的年龄中位数为59岁（四分位间距：55 - 62岁），男性40名。与基线相比，三组的FBG均显著降低。此外，干预后MN-Gup-GOS组的HbA1c、血清胰岛素和HOMA-IR显著降低，而安慰剂组和MN-Gup组未观察到此类降低。组间比较显示，与安慰剂组（最小二乘均值差异[95%CI]，-0.69[-1.29，-0.10]mmol/L，P = 0.022）和MN-Gup组（-0.59[-1.17，-0.01]，P = 0.047）相比，MN-Gup-GOS干预使FBG降低更为显著，但对其他糖代谢指标无此效果。此外，MN-Gup和MN-Gup-GOS干预，尤其是后者，显著改变了炎症、氧化应激、肠道微生物群、血清BAs和胰高血糖素样肽-1（GLP-1）水平。相关性分析显示，某些肠道微生物群（双歧杆菌）和BAs（脱氧胆酸和石胆酸）的变化与血糖指标之间存在显著关联。
在T2DM患者中，合生元MN-Gup-GOS降低FBG水平的辅助作用超过单独使用MN-Gup益生菌，这可能归因于对肠道微生物群、BAs和GLP-1分泌的调节增强。
