维生素 K2 补充剂通过肠道微生物组和粪便代谢物改善 2 型糖尿病患者受损的血糖稳态和胰岛素敏感性。
Vitamin K2 supplementation improves impaired glycemic homeostasis and insulin sensitivity for type 2 diabetes through gut microbiome and fecal metabolites.
机构信息
Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, China.
Department of Nutrition, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.
出版信息
BMC Med. 2023 May 5;21(1):174. doi: 10.1186/s12916-023-02880-0.
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).
背景
目前维生素 K2 通过调节肠道微生物组成来改善 2 型糖尿病症状的能力的证据还不充分。在此，我们旨在证明维生素 K2 干预可通过改善肠道微生物群来改善受损的血糖稳态和胰岛素敏感性。
方法
我们首先对 60 名 T2DM 患者进行了为期 6 个月的 RCT 研究，其中一些患者接受了 MK-7（一种天然形式的维生素 K2）干预，另一些患者未接受干预。此外，我们还对饮食诱导肥胖小鼠进行了为期 4 周的 MK-7 调节菌群移植。在这两个研究阶段，我们都使用 16S rRNA 测序、粪便代谢组学和转录组学来阐明潜在的机制。
结果
在 MK-7 干预后，我们观察到 2 型糖尿病患者空腹血糖（P=0.048）、胰岛素（P=0.005）和 HbA1c 水平分别显著降低 13.4%、28.3%和 7.4%，并且饮食诱导肥胖小鼠的葡萄糖耐量也显著改善（P=0.005）。此外，我们发现人类和小鼠粪便中的次级胆汁酸（石胆酸和牛磺脱氧胆酸）和短链脂肪酸（乙酸、丁酸和缬草酸）浓度增加，同时这些代谢物的生物合成相关菌属的丰度也增加。最后，我们发现，4 周的粪便微生物群移植通过激活结肠胆汁酸受体、改善宿主免疫炎症反应和增加循环 GLP-1 浓度，显著改善了饮食诱导肥胖小鼠的葡萄糖耐量。
结论
我们的肠道相关发现为维生素 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 干预在糖尿病管理中的临床应用。
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