Vitamin K2 Supplementation Improve Impaired Glycemic Homeostasis and Insulin Sensitivity for Type 2 Diabetes through Gut Microbiome and Fecal Metabolites

There is insufficient evidence for the ability of vitamin K2 to improve type 2 diabetes mellitus symptoms by regulating gut microbial composition. Here, we demonstrated that improved glycemic homeostasis and insulin sensitivity were closely correlated with changes in the gut microbiota and its metabolites following intervention with MK-7 (a natural form of vitamin K2 with a longer half-life). After MK-7 intervention, the microbiota exhibited increased biosynthesis of gut short-chain fatty acids, secondary bile acids, and circulating glucagon-like peptide-1 and ameliorated inflammatory immune responses in liver, colon and pancreas tissues. After fecal microbial transplantation with the MK-7-regulated gut microbiota, the improvement in impaired glucose metabolism in obese mice was comparable to that after transplantation of the gut microbiota from lean donors. These findings highlight the benefits of vitamin K2 supplementation in diabetic patients, revealing novel gut-dependent effects of MK-7 on glycemic homeostasis and benefits for both the host and the microbiota.目前尚无充分证据表明维生素K2（vitamin K2）可通过调控肠道微生物组（gut microbiota）组成改善2型糖尿病（type 2 diabetes mellitus）症状。本研究证实，经MK-7（一种半衰期更长的天然维生素K2形式）干预后，宿主血糖稳态与胰岛素敏感性的改善与肠道微生物组及其代谢物的变化密切相关。MK-7干预后，肠道微生物组的短链脂肪酸（short-chain fatty acids）、次级胆汁酸（secondary bile acids）生物合成能力显著提升，循环中胰高血糖素样肽-1（glucagon-like peptide-1）水平升高，同时可缓解肝脏、结肠及胰腺组织的炎症免疫应答。将MK-7调控后的肠道微生物群进行粪便微生物群移植（fecal microbial transplantation）后，肥胖小鼠受损糖代谢的改善效果与移植瘦型供体肠道微生物群的效果相当。本研究结果凸显了补充维生素K2对糖尿病患者的益处，揭示了MK-7依赖肠道的新型血糖稳态调控作用，以及其对宿主与肠道微生物组的双重益处。