DataSheet1_Ginsenoside Rb1 ameliorates Glycemic Disorder in Mice With High Fat Diet-Induced Obesity via Regulating Gut Microbiota and Amino Acid Metabolism.docx

Accumulating evidences suggested an association between gut microbiome dysbiosis and impaired glycemic control. Ginsenoside Rb1 (Rb1) is a biologically active substance of ginseng, which serves anti-diabetic effects. However, its working mechanism especially interaction with gut microbes remains elusive in detail. In this study, we investigated the impact of Rb1 oral supplementation on high fat diet (HFD) induced obesity mice, and explored its mechanism in regulating blood glucose. The results showed that higher liver weight and lower cecum weight were observed in HFD fed mice, which was maintained by Rb1 administration. In addition, Rb1 ameliorated HFD induced blood lipid abnormality and improved insulin sensitivity. Several mRNA expressions in the liver were measured by quantitative real-time PCR, of which UCP2, Nr1H4, and Fiaf were reversed by Rb1 treatment. 16S rRNA sequencing analysis indicated that Rb1 significantly altered gut microbiota composition and increased the abundance of mucin-degrading bacterium Akkermansia spp. compared to HFD mice. As suggested via functional prediction, amino acid metabolism was modulated by Rb1 supplementation. Subsequent serum amino acids investigation indicated that several diabetes associated amino acids, like branched-chain amino acids, tryptophan and alanine, were altered in company with Rb1 supplementation. Moreover, correlation analysis firstly implied that the circulation level of alanine was related to Akkermansia spp.. In summary, Rb1 supplementation improved HFD induced insulin resistance in mice, and was associated with profound changes in microbial composition and amino acid metabolism.

累积的证据表明，肠道菌群失调与血糖控制障碍之间存在关联。人参皂苷Rb1（Rb1）是人参中的一种生物活性物质，具有抗糖尿病的作用。然而，其作用机制，尤其是与肠道微生物的相互作用，在细节上仍不明确。在本研究中，我们探讨了Rb1口服补充剂对高脂饮食（HFD）诱导的肥胖小鼠的影响，并探索了其在调节血糖方面的机制。结果显示，在高脂饮食喂养的小鼠中观察到肝脏重量增加和盲肠重量减少，而Rb1的给予则维持了这一状态。此外，Rb1改善了HFD诱导的血脂异常并提高了胰岛素敏感性。通过定量实时PCR测量了肝脏中几种mRNA的表达，其中UCP2、Nr1H4和Fiaf的表达在Rb1治疗后得到逆转。16S rRNA测序分析表明，与HFD小鼠相比，Rb1显著改变了肠道菌群组成，并增加了粘蛋白降解菌Akkermansia spp.的丰度。功能预测表明，氨基酸代谢受到Rb1补充剂的调节。后续的血清氨基酸研究显示，与Rb1补充剂伴随的是一些与糖尿病相关的氨基酸，如支链氨基酸、色氨酸和丙氨酸发生了改变。此外，相关性分析首次表明，丙氨酸的循环水平与Akkermansia spp.相关。总之，Rb1补充剂改善了小鼠因高脂饮食引起的胰岛素抵抗，并与微生物组成和氨基酸代谢的深刻变化相关。