Section for Nutrition Research, Department of Medicine, Imperial College London, London, UK.
Stable Isotope Biochemistry Laboratory, Scottish Universities Environmental Research Centre, Glasgow, UK.
Gut. 2019 Aug;68(8):1430-1438. doi: 10.1136/gutjnl-2019-318424. Epub 2019 Apr 10.
To investigate the underlying mechanisms behind changes in glucose homeostasis with delivery of propionate to the human colon by comprehensive and coordinated analysis of gut bacterial composition, plasma metabolome and immune responses.
Twelve non-diabetic adults with overweight and obesity received 20 g/day of inulin-propionate ester (IPE), designed to selectively deliver propionate to the colon, a high-fermentable fibre control (inulin) and a low-fermentable fibre control (cellulose) in a randomised, double-blind, placebo-controlled, cross-over design. Outcome measurements of metabolic responses, inflammatory markers and gut bacterial composition were analysed at the end of each 42-day supplementation period.
Both IPE and inulin supplementation improved insulin resistance compared with cellulose supplementation, measured by homeostatic model assessment 2 (mean±SEM 1.23±0.17 IPE vs 1.59±0.17 cellulose, p=0.001; 1.17±0.15 inulin vs 1.59±0.17 cellulose, p=0.009), with no differences between IPE and inulin (p=0.272). Fasting insulin was only associated positively with plasma tyrosine and negatively with plasma glycine following inulin supplementation. IPE supplementation decreased proinflammatory interleukin-8 levels compared with cellulose, while inulin had no impact on the systemic inflammatory markers studied. Inulin promoted changes in gut bacterial populations at the class level (increased Actinobacteria and decreased Clostridia) and order level (decreased Clostridiales) compared with cellulose, with small differences at the species level observed between IPE and cellulose.
These data demonstrate a distinctive physiological impact of raising colonic propionate delivery in humans, as improvements in insulin sensitivity promoted by IPE and inulin were accompanied with different effects on the plasma metabolome, gut bacterial populations and markers of systemic inflammation.
通过全面协调地分析肠道细菌组成、血浆代谢组和免疫反应，研究向人体结肠输送丙酸导致葡萄糖稳态变化的潜在机制。
12 名超重和肥胖的非糖尿病成年人接受 20g/天的菊粉-丙酸酯（IPE），旨在选择性地将丙酸输送到结肠，一种高发酵纤维对照物（菊粉）和一种低发酵纤维对照物（纤维素），采用随机、双盲、安慰剂对照、交叉设计。在每个 42 天补充期结束时分析代谢反应、炎症标志物和肠道细菌组成的结果测量。
IPE 和菊粉补充均改善了胰岛素抵抗，与纤维素补充相比，通过稳态模型评估 2 测量（平均±SEM：IPE 为 1.23±0.17，而纤维素为 1.59±0.17，p=0.001；菊粉为 1.17±0.15，而纤维素为 1.59±0.17，p=0.009），IPE 和菊粉之间没有差异（p=0.272）。仅在补充菊粉后，空腹胰岛素与血浆酪氨酸呈正相关，与血浆甘氨酸呈负相关。与纤维素相比，IPE 补充降低了促炎细胞因子白细胞介素-8 的水平，而菊粉对所研究的系统炎症标志物没有影响。与纤维素相比，菊粉促进了类水平（增加的放线菌和减少的梭菌）和目水平（减少的梭状芽孢杆菌）的肠道细菌种群的变化，在 IPE 和纤维素之间观察到物种水平的微小差异。
这些数据表明，在人类中提高结肠丙酸输送具有独特的生理影响，IPE 和菊粉促进胰岛素敏感性的改善伴随着不同的血浆代谢组、肠道细菌种群和全身炎症标志物的影响。
