Institute of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha,410008, China; Hunan Key Laboratory of Traditional Chinese Medicine for Gan of State Administration, Central South University, Changsha, 410008, China.
Institute of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha,410008, China; Hunan Key Laboratory of Traditional Chinese Medicine for Gan of State Administration, Central South University, Changsha, 410008, China.
Phytomedicine. 2020 Oct;77:153268. doi: 10.1016/j.phymed.2020.153268. Epub 2020 Jun 30.
Cyclocarya paliurus polysaccharide (CCPP), a primary active component in the leaves of Cyclocarya paliurus (Batal.) Iljinsk (C. paliurus), has the ability to treat type 2 diabetes mellitus (T2DM), but cannot be digested by our digestive system. Therefore, mechanisms of regulating the gut microbiota and intestinal metabolites might exist.
To reveal the potential mechanism of CCPP treatment, this study aimed to investigate the alterations of the gut microbiota and intestinal metabolites especially short chain fatty acids (SCFAs) in type 2 diabetic rats.
Type 2 diabetic rat models were developed, and the therapeutic effects of CCPP were evaluated. Metagenomics analysis was utilized to analyze the alterations to the gut microbiota, and UHPLC-QTOF/MS-based untargeted metabolomics analysis of colon contents was used to identify the differential intestinal metabolites. GC/MS was used to measure the SCFAs in rat's colon contents and human fecal inoculums. Furthermore, the expression of SCFA receptors including GPR41, GPR43 and GPR109a was verified by qRT-PCR and the concentration of glucagon-like peptide-1(GLP-1) and peptide tyrosinetyrosine (PYY) was measured by Elisa.
Inhibition of the blood glucose levels and improvements in glucose tolerance and serum lipid parameters were observed after CCPP treatment. Eleven SCFA-producing species including Ruminococcus_bromii, Anaerotruncus_colihominis, Clostridium_methylpentosum, Roseburia_intestinalis, Roseburia_hominis, Clostridium_asparagiforme, Pseudoflavonifractor_capillosus, Intestinimonas_butyriciproducens, Intestinimonas_sp._GD2, Oscillibacter_valericigenes and Oscillibacter_ruminantium were clearly increased in the CCPP group. Furthermore, our study indicated that CCPP increases the production of SCFAs both in vivo and in vitro, and the gut microbiota are the key factor of this process. The SCFA receptors including GPR41, GPR43 and GPR109a, were significantly stimulated in the CCPP treated rats, which was accompanied by the upregulated expression of GLP-1 and PYY.
These results demonstrated that CCPP could alleviate type 2 diabetic symptoms by increasing the SCFA-producing bacteria, promoting the production of SCFAs and upregulating SCFA-GLP1/PYY associated sensory mediators.
青钱柳叶多糖（CCPP）是青钱柳（Cyclocarya paliurus）（C. paliurus）叶子中的主要活性成分之一，具有治疗 2 型糖尿病（T2DM）的能力，但不能被我们的消化系统消化。因此，可能存在调节肠道微生物群和肠道代谢物的机制。
为了揭示 CCPP 治疗的潜在机制，本研究旨在研究 2 型糖尿病大鼠肠道微生物群和肠道代谢物（特别是短链脂肪酸（SCFAs））的变化。
建立 2 型糖尿病大鼠模型，并评估 CCPP 的治疗效果。利用宏基因组学分析来分析肠道微生物群的变化，并用 UHPLC-QTOF/MS 基于非靶向代谢组学分析结肠内容物以鉴定差异肠道代谢物。GC/MS 用于测量大鼠结肠内容物和人粪便接种物中的 SCFAs。此外，通过 qRT-PCR 验证了 SCFA 受体（包括 GPR41、GPR43 和 GPR109a）的表达，并通过 Elisa 测量了胰高血糖素样肽-1（GLP-1）和肽酪氨酸酪氨酸（PYY）的浓度。
CCPP 治疗后，观察到血糖水平抑制、葡萄糖耐量改善和血清脂质参数改善。11 种产生 SCFA 的物种，包括 Ruminococcus_bromii、Anaerotruncus_colihominis、Clostridium_methylpentosum、Roseburia_intestinalis、Roseburia_hominis、Clostridium_asparagiforme、Pseudoflavonifractor_capillosus、Intestinimonas_butyriciproducens、Intestinimonas_sp._GD2、Oscillibacter_valericigenes 和 Oscillibacter_ruminantium，在 CCPP 组中明显增加。此外，我们的研究表明，CCPP 增加了体内和体外 SCFA 的产生，而肠道微生物群是这一过程的关键因素。在 CCPP 治疗的大鼠中，SCFA 受体（包括 GPR41、GPR43 和 GPR109a）明显受到刺激，同时 GLP-1 和 PYY 的表达上调。
这些结果表明，CCPP 可以通过增加产生 SCFA 的细菌、促进 SCFA 的产生和上调与 SCFA-GLP1/PYY 相关的感觉介质来缓解 2 型糖尿病症状。
