PDF(Pubmed)
Abstract：
There is insufficient evidence for the ability of vitamin K2 to improve type 2 diabetes mellitus symptoms by regulating gut microbial composition. Herein, we aimed to demonstrate the key role of the gut microbiota in the improvement of impaired glycemic homeostasis and insulin sensitivity by vitamin K2 intervention.
We first performed a 6-month RCT on 60 T2DM participants with or without MK-7 (a natural form of vitamin K2) intervention. In addition, we conducted a transplantation of the MK-7-regulated microbiota in diet-induced obesity mice for 4 weeks. 16S rRNA sequencing, fecal metabolomics, and transcriptomics in both study phases were used to clarify the potential mechanism.
After MK-7 intervention, we observed notable 13.4%, 28.3%, and 7.4% reductions in fasting serum glucose (P = 0.048), insulin (P = 0.005), and HbA1c levels (P = 0.019) in type 2 diabetes participants and significant glucose tolerance improvement in diet-induced obesity mice (P = 0.005). Moreover, increased concentrations of secondary bile acids (lithocholic and taurodeoxycholic acid) and short-chain fatty acids (acetic acid, butyric acid, and valeric acid) were found in human and mouse feces accompanied by an increased abundance of the genera that are responsible for the biosynthesis of these metabolites. Finally, we found that 4 weeks of fecal microbiota transplantation significantly improved glucose tolerance in diet-induced obesity mice by activating colon bile acid receptors, improving host immune-inflammatory responses, and increasing circulating GLP-1 concentrations.
Our gut-derived findings provide evidence for a regulatory role of vitamin K2 on glycemic homeostasis, which may further facilitate the clinical implementation of vitamin K2 intervention for diabetes management.
The study was registered at https://www.chictr.org.cn (ChiCTR1800019663).
We first performed a 6-month RCT on 60 T2DM participants with or without MK-7 (a natural form of vitamin K2) intervention. In addition, we conducted a transplantation of the MK-7-regulated microbiota in diet-induced obesity mice for 4 weeks. 16S rRNA sequencing, fecal metabolomics, and transcriptomics in both study phases were used to clarify the potential mechanism.
After MK-7 intervention, we observed notable 13.4%, 28.3%, and 7.4% reductions in fasting serum glucose (P = 0.048), insulin (P = 0.005), and HbA1c levels (P = 0.019) in type 2 diabetes participants and significant glucose tolerance improvement in diet-induced obesity mice (P = 0.005). Moreover, increased concentrations of secondary bile acids (lithocholic and taurodeoxycholic acid) and short-chain fatty acids (acetic acid, butyric acid, and valeric acid) were found in human and mouse feces accompanied by an increased abundance of the genera that are responsible for the biosynthesis of these metabolites. Finally, we found that 4 weeks of fecal microbiota transplantation significantly improved glucose tolerance in diet-induced obesity mice by activating colon bile acid receptors, improving host immune-inflammatory responses, and increasing circulating GLP-1 concentrations.
Our gut-derived findings provide evidence for a regulatory role of vitamin K2 on glycemic homeostasis, which may further facilitate the clinical implementation of vitamin K2 intervention for diabetes management.
The study was registered at https://www.chictr.org.cn (ChiCTR1800019663).
摘要：
背景：没有足够的证据表明维生素K2能够通过调节肠道微生物组成来改善2型糖尿病症状。在这里，我们旨在证明肠道菌群在通过维生素K2干预改善受损的血糖稳态和胰岛素敏感性中的关键作用.
方法：我们首先对60名有或没有MK-7（一种天然形式的维生素K2）干预的T2DM参与者进行了为期6个月的RCT。此外,我们在饮食诱导的肥胖小鼠中进行了MK-7调节的微生物群移植4周。16SrRNA测序，粪便代谢组学，和转录组学在两个研究阶段都被用来阐明潜在的机制。
结果：MK-7干预后，我们观察到13.4%，28.3%,空腹血糖下降7.4%（P=0.048），胰岛素（P=0.005），2型糖尿病参与者的HbA1c水平（P=0.019）和饮食诱导的肥胖小鼠的葡萄糖耐量显着改善（P=0.005）。此外，次级胆汁酸（石胆酸和牛磺脱氧胆酸）和短链脂肪酸（乙酸，丁酸,和戊酸）在人和小鼠粪便中发现，伴随着负责这些代谢物生物合成的属的丰度增加。最后,我们发现4周的粪便微生物移植通过激活结肠胆汁酸受体显著改善饮食诱导的肥胖小鼠的葡萄糖耐量,改善宿主免疫炎症反应，和增加循环GLP-1浓度。
结论：我们的肠道研究结果为维生素K2对血糖稳态的调节作用提供了证据，这可能进一步促进维生素K2干预糖尿病管理的临床实施。
背景：该研究在https://www注册。chictr.org.cn(ChiCTR1800019663)。
方法：我们首先对60名有或没有MK-7（一种天然形式的维生素K2）干预的T2DM参与者进行了为期6个月的RCT。此外,我们在饮食诱导的肥胖小鼠中进行了MK-7调节的微生物群移植4周。16SrRNA测序，粪便代谢组学，和转录组学在两个研究阶段都被用来阐明潜在的机制。
结果：MK-7干预后，我们观察到13.4%，28.3%,空腹血糖下降7.4%（P=0.048），胰岛素（P=0.005），2型糖尿病参与者的HbA1c水平（P=0.019）和饮食诱导的肥胖小鼠的葡萄糖耐量显着改善（P=0.005）。此外，次级胆汁酸（石胆酸和牛磺脱氧胆酸）和短链脂肪酸（乙酸，丁酸,和戊酸）在人和小鼠粪便中发现，伴随着负责这些代谢物生物合成的属的丰度增加。最后,我们发现4周的粪便微生物移植通过激活结肠胆汁酸受体显著改善饮食诱导的肥胖小鼠的葡萄糖耐量,改善宿主免疫炎症反应，和增加循环GLP-1浓度。
结论：我们的肠道研究结果为维生素K2对血糖稳态的调节作用提供了证据，这可能进一步促进维生素K2干预糖尿病管理的临床实施。
背景：该研究在https://www注册。chictr.org.cn(ChiCTR1800019663)。
