PMID- 32937246 OWN - NLM STAT- MEDLINE DCOM- 20210218 LR - 20210218 IS - 1950-6007 (Electronic) IS - 0753-3322 (Linking) VI - 131 DP - 2020 Nov TI - Berberine alleviates type 2 diabetic symptoms by altering gut microbiota and reducing aromatic amino acids. PG - 110669 LID - S0753-3322(20)30862-3 [pii] LID - 10.1016/j.biopha.2020.110669 [doi] AB - OBJECTIVE: Berberine (BBR), which is extracted from traditional Chinese herb, is abundant in Coptis chinensis and Berberis vulgaris, with a treatment on type 2 diabetes mellitus (T2DM). However, its oral bioavailability is poor. Therefore, the ability of BBR to regulate gut microbiota and intestinal metabolites might exist. This study aimed to investigate changes in gut microbiota and intestinal metabolites, and to reveal the potential mechanism of BBR. METHODS: To observe the role of gut microbiota in the treatment of T2DM by BBR, antibiotics intervened gut microbiota was used in this study, and the therapeutic effects of BBR were evaluated. A 16S rRNA gene sequencing approach was utilized to analyze gut microbiota alterations, and UHPLC-QTOF/MS-based untargeted metabolomics analysis of colon contents was used to identity differential intestinal metabolites. Finally, serum aromatic amino acids (AAAs) were absolutely quantified using LC/MS. RESULTS: Inhibition of the blood glucose levels, and improvements in glucose tolerance and serum lipid parameters were observed in the BBR treated group. Type 2 diabetic symptoms in rats in the BA group (treated with antibotics and BBR) were alleviated. However, the therapeutical effects are weaker in the BA group compared with the BBR group, indicating that BBR can be used to treat type 2 diabetic rats immediately, and modulation of gut microbiota is related to the mechanism of BBR in the treatment of T2DM. The community richness and diversity of the gut microbiota were significantly increased by BBR, and the relative abundance of Bacteroidetes was increased in the BBR group, which was accompanied by a decreased relative abundance of Proteobacteria and Verrucomicrobia at the phylum level. At the family level, a probiotic Lactobacillaceae was significantly upregulated not only in the BBR group but also in the BA group and was negatively associated with the risk of T2DM. Metabolomic analysis of colon contents identified 55 differential intestinal metabolites between the BBR group and the model group. AAAs, including tyrosine, tryptophan and phenylalanine, were obviously decreased in the BBR group not only in the colon contents but also in the serum. CONCLUSIONS: These results demonstrated that BBR could alleviate symptoms in type 2 diabetic rats by affecting gut microbiota composition and reducing the concentration of AAAs. CI - Copyright (c) 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved. FAU - Yao, Ye AU - Yao Y AD - 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: xyyaoye@csu.edu.cn. FAU - Chen, Han AU - Chen H AD - 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: xyhanchen@aliyun.com. FAU - Yan, Lijing AU - Yan L AD - 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: xylijingyan@163.com. FAU - Wang, Wenbo AU - Wang W AD - 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: wangwenbo@csu.edu.cn. FAU - Wang, Dongsheng AU - Wang D AD - 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. LA - eng PT - Journal Article DEP - 20200913 PL - France TA - Biomed Pharmacother JT - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JID - 8213295 RN - 0 (Amino Acids, Aromatic) RN - 0I8Y3P32UF (Berberine) SB - IM MH - Amino Acids, Aromatic/*antagonists & inhibitors/metabolism MH - Animals MH - Berberine/pharmacology/*therapeutic use MH - Diabetes Mellitus, Experimental/*drug therapy/metabolism MH - Diabetes Mellitus, Type 2/*drug therapy/metabolism MH - Gastrointestinal Microbiome/*drug effects/physiology MH - Male MH - Random Allocation MH - Rats MH - Rats, Sprague-Dawley OTO - NOTNLM OT - 16S rRNA gene sequencing OT - AAAs OT - Berberine OT - Gut microbiota OT - Metabolomics OT - T2DM EDAT- 2020/09/17 06:00 MHDA- 2021/02/20 06:00 CRDT- 2020/09/16 20:09 PHST- 2020/05/23 00:00 [received] PHST- 2020/08/14 00:00 [revised] PHST- 2020/08/20 00:00 [accepted] PHST- 2020/09/17 06:00 [pubmed] PHST- 2021/02/20 06:00 [medline] PHST- 2020/09/16 20:09 [entrez] AID - S0753-3322(20)30862-3 [pii] AID - 10.1016/j.biopha.2020.110669 [doi] PST - ppublish SO - Biomed Pharmacother. 2020 Nov;131:110669. doi: 10.1016/j.biopha.2020.110669. Epub 2020 Sep 13.