肠道菌群
医学
内科学
2型糖尿病
内分泌学
葡萄糖稳态
胆汁酸
血糖性
胆酸
2型糖尿病
胰岛素抵抗
胰岛素
糖尿病
微生物群
生物
免疫学
生物信息学
作者
Yuntao Zhang,Lin Liu,Chunbo Wei,Xuanyang Wang,Ran Li,Xiaoqing Xu,Yingfeng Zhang,Guannan Geng,Keke Dang,Minghui Zhu,Xinmiao Tao,Huan Xu,Xuemin Yan,Jia Zhang,Jinxia Hu,Ying Liu
出处
期刊:BMC Medicine
[Springer Nature]
日期:2023-05-05
卷期号:21 (1)
被引量:3
标识
DOI:10.1186/s12916-023-02880-0
摘要
Abstract Background 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. Methods 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. Results 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. Conclusions 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. Trial registration The study was registered at https://www.chictr.org.cn (ChiCTR1800019663).
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