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调节 2 型糖尿病大鼠粪便中的肠道微生物群和短链脂肪酸可能是罗汉果果实中罗汉果苷的降血糖机制之一。

Regulating the gut microbiota and SCFAs in the faeces of T2DM rats should be one of antidiabetic mechanisms of mogrosides in the fruits of Siraitia grosvenorii.

机构信息

School of Pharmacy, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Minhang District, Shanghai, 200240, China.

School of Pharmacy, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Minhang District, Shanghai, 200240, China.

出版信息

J Ethnopharmacol. 2021 Jun 28;274:114033. doi: 10.1016/j.jep.2021.114033. Epub 2021 Mar 17.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

The Siraitia grosvenorii fruits extract (SG, in which mogrosides are the main components), considered as a non-nutritional sweetener, has an antidiabetic effect. Our previous studies have confirmed that an extract of mogrosides being rich in triterpene glycosides with 1-3 glucosyl residues, designated as low-polar S. grosvenorii glycosides (L-SGgly), had a significant antidiabetic effect. However, whether the mechanism through impacting on gut microbiota to exert the antidiabetic effect of mogrosides remains unclear.

AIMS OF THE STUDY

To explore the potential mechanism of mogrosides (SG and L-SGgly) on gut microbiota and faecal metabolites in the treatment of diabetes.

STUDY DESIGN AND METHODS

In this study, the effects of SG and L-SGgly on gut microbiota and faecal endogenous metabolites were explored by sequencing the 16S rRNA V3-V4 region of gut microbiota, and detecting with gas chromatography-mass spectrometry (GC-MS) and liquid chromatography quadrupole time-of-flight MS (LC-Q-TOF/MS), respectively. In particular, correlation analyses revealed how these influences affect the anti-hyperglycaemic effect, to give the underlying antidiabetic mechanisms of the mogrosides in S. grosvenorii fruits.

RESULTS

After a 14-day treatment with SG and L-SGgly for type 2 diabetes mellitus (T2DM) rats induced by a high-fat diet (HFD) and streptozotocin (STZ), the disordered gut microbiota in the faeces of T2DM rats were recovered. At the same time, the short-chain fatty acids (SCFAs) concentration significantly increased and the deoxycholic acid and 1β-hydroxycholic acid content decreased in the faeces of T2DM rats. Moreover, correlation analyses provided the evidences that gut microbiota and its metabolites could be the target for exerting the anti-hyperglycaemic effects of SG and L-SGgly. Especially, Elusimicrobium, Lachnospiraceae_UCG-004, acetate, butyrate, and 1β-hydroxycholic acid would be the potential dominant bacteria and biomarkers for SG and L-SGgly in reducing the blood glucose and insulin resistance of T2DM rats.

CONCLUSION

It is the first time that a mechanism of targeting on gut microbiota for the antidiabetic effect of mogrosides in S. grosvenorii fruits has been proposed.

摘要

民族药理学相关性

罗汉果果实提取物(SG,其中主要成分为罗汉果甜苷)被认为是一种非营养性甜味剂,具有降血糖作用。我们之前的研究证实,一种富含 1-3 个葡萄糖基的三萜糖苷的罗汉果甜苷提取物,命名为低极性罗汉果糖苷(L-SGgly),具有显著的降血糖作用。然而,通过影响肠道微生物群发挥罗汉果甜苷降血糖作用的机制尚不清楚。

研究目的

探讨罗汉果甜苷(SG 和 L-SGgly)对糖尿病治疗中肠道微生物群和粪便内源性代谢物的潜在作用机制。

研究设计和方法

本研究通过对肠道微生物群 16S rRNA V3-V4 区进行测序,分别采用气相色谱-质谱联用(GC-MS)和液相色谱四极杆飞行时间质谱联用(LC-Q-TOF/MS)检测,探讨 SG 和 L-SGgly 对肠道微生物群和粪便内源性代谢物的影响。特别地,相关性分析揭示了这些影响如何影响抗高血糖作用,从而为罗汉果果实中罗汉果甜苷的降血糖机制提供依据。

结果

经过 14 天的高脂饮食(HFD)和链脲佐菌素(STZ)诱导的 2 型糖尿病(T2DM)大鼠用 SG 和 L-SGgly 治疗后,T2DM 大鼠粪便中紊乱的肠道微生物群得到恢复。同时,粪便中短链脂肪酸(SCFAs)浓度显著增加,脱氧胆酸和 1β-羟基胆酸含量降低。此外,相关性分析提供了证据表明,肠道微生物群及其代谢物可能是 SG 和 L-SGgly 发挥抗高血糖作用的靶点。特别是,Elusimicrobium、Lachnospiraceae_UCG-004、醋酸盐、丁酸盐和 1β-羟基胆酸可能是 SG 和 L-SGgly 降低 T2DM 大鼠血糖和胰岛素抵抗的潜在优势细菌和生物标志物。

结论

这是首次提出罗汉果果实中罗汉果甜苷的降血糖作用机制是靶向肠道微生物群。

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