Ye Yao1, Lijing Yan1, Han Chen1, Ning Wu1, Wenbo Wang1, Dongsheng Wang2. 1. 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. 2. 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. Electronic address: wdsh666@126.com.
Abstract
BACKGROUND: 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. PURPOSE: 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. STUDY DESIGN AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: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. PURPOSE: 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 diabeticrats. STUDY DESIGN AND METHODS: Type 2 diabeticrat 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. RESULTS: 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. CONCLUSION: 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.