PMID- 35857109 OWN - NLM STAT- MEDLINE DCOM- 20220826 LR - 20220826 IS - 1432-5233 (Electronic) IS - 0940-5429 (Linking) VI - 59 IP - 10 DP - 2022 Oct TI - The potential mechanism of Liu-Wei-Di-Huang Pills in treatment of type 2 diabetic mellitus: from gut microbiota to short-chain fatty acids metabolism. PG - 1295-1308 LID - 10.1007/s00592-022-01922-y [doi] AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) has already become a global pandemic. Recently, reports showed its pathogenesis was closely related to a disorder of gut microbiota. In China, the Liu-Wei-Di-Huang Pills (LWDH) have treated T2DM for thousands of years. However, its therapeutic mechanism associated with gut microbiota is worthy of further study. AIMS: This study aims to investigate the effects of LWDH on T2DM by regulating gut microbiota and short-chain fatty acids (SCFAs) in Goto-Kakizaki (GK) rats. METHODS: T2DM models were successfully established based on GK rats and administrated with LWDH. The changes in fasting blood glucose (FBG), oral glucose tolerance test (OGTT), and serum insulin (INS) were determined, and the immunohistochemical (IHC) method was used to test INS expression in pancreas. The 16S-ribosomal DNA (16S rDNA) sequencing analysis assessed gut microbiota structural changes; a gas chromatography-mass spectrometer (GC-MS)-based metabolomics method was adopted to detect SCFA levels. The pathological morphology of jejunum was detected by hematoxylin-eosin (H&E) staining, and the expression of GPR43, GPR41, GLP-1, and GLP-1R was evaluated by qRT-PCR and ELISA, respectively. RESULTS: We observed that GK rats treated with LWDH: (a) has altered the microbial structure and promoted the abundance of bacteria in Firmicutes, including Lactobacillus, Allobaculum, and Ruminococcus_2, (b) increased SCFAs levels involving acetic acid, propionic acid, and butyric acid and (c) alleviated T2DM and jejunum injuries potentially based on SCFAs-GPR43/41-GLP-1 pathway. CONCLUSION: LWDH could improve T2DM by regulating gut microbiota and SCFAs, and the therapeutic mechanism might be related to the SCFAs-GPR43/41-GLP-1 pathway. CI - (c) 2022. Springer-Verlag Italia S.r.l., part of Springer Nature. FAU - Yi, Zi-Yang AU - Yi ZY AUID- ORCID: 0000-0002-2589-2135 AD - Hunan Academy of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410013, Hunan, People's Republic of China. FAU - Chen, Lin AU - Chen L AD - Hunan Academy of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410013, Hunan, People's Republic of China. FAU - Wang, Yan AU - Wang Y AD - H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan. FAU - He, Dan AU - He D AD - Hunan Academy of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410013, Hunan, People's Republic of China. FAU - Zhao, Di AU - Zhao D AD - Hunan Academy of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410013, Hunan, People's Republic of China. FAU - Zhang, Shui-Han AU - Zhang SH AD - Hunan Academy of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410013, Hunan, People's Republic of China. FAU - Yu, Rong AU - Yu R AD - Hunan Academy of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410013, Hunan, People's Republic of China. 002165@hnucm.edu.cn. AD - Hunan Key Laboratory of TCM Prescription and Syndromes Translational Medicine, Hunan University of Chinese Medicine, Changsha, 410208, Hunan, People's Republic of China. 002165@hnucm.edu.cn. FAU - Huang, Jian-Hua AU - Huang JH AD - Hunan Academy of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410013, Hunan, People's Republic of China. huangjianhua1985@163.com. AD - Hunan Key Laboratory of TCM Prescription and Syndromes Translational Medicine, Hunan University of Chinese Medicine, Changsha, 410208, Hunan, People's Republic of China. huangjianhua1985@163.com. LA - eng GR - 2020JJ5325/Natural Science Foundation of Hunan Province/ GR - No. 82074400/National Nature Science Foundation of China/ GR - U21A20411/National Nature Science Foundation of China/ GR - 2020JJ5325/Natural Science Foundation of Hunan Province/ GR - 2020ZYQ038/Key Research and Development Project of Hunan Province Science and Technology/ GR - 2020SK2029/Key Research and Development Project of Hunan Province Science and Technology/ GR - 2020SK2101/Key Research and Development Project of Hunan Province Science and Technology/ GR - kh2004018/Project of Changsha Technology Innovation Center/ GR - kq1802017/Training Program for Excellent Young Innovators of Changsha/ GR - 202092/Research Project of Traditional Chinese Medicine Bureau of Hunan Province/ GR - [2017]66/Program of Survey of Chinese Medicines of China/ GR - 2060302/Research on the Comprehensive Development and Utilization of Characteristic Traditional Chinese Medicine Resources/ PT - Journal Article DEP - 20220720 PL - Germany TA - Acta Diabetol JT - Acta diabetologica JID - 9200299 RN - 0 (Fatty Acids, Volatile) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Animals MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Fatty Acids, Volatile MH - *Gastrointestinal Microbiome MH - Glucagon-Like Peptide 1/therapeutic use MH - Lipid Metabolism MH - Rats OTO - NOTNLM OT - G-protein-coupled receptors 41 OT - G-protein-coupled receptors 43 OT - Glucagon-like peptide-1 OT - Metabolomics OT - Microbiome OT - Short-chain fatty acids EDAT- 2022/07/21 06:00 MHDA- 2022/08/27 06:00 CRDT- 2022/07/20 11:15 PHST- 2022/02/22 00:00 [received] PHST- 2022/06/11 00:00 [accepted] PHST- 2022/07/21 06:00 [pubmed] PHST- 2022/08/27 06:00 [medline] PHST- 2022/07/20 11:15 [entrez] AID - 10.1007/s00592-022-01922-y [pii] AID - 10.1007/s00592-022-01922-y [doi] PST - ppublish SO - Acta Diabetol. 2022 Oct;59(10):1295-1308. doi: 10.1007/s00592-022-01922-y. Epub 2022 Jul 20.