PMID- 31744910 OWN - NLM STAT- MEDLINE DCOM- 20210216 LR - 20210216 IS - 1468-3288 (Electronic) IS - 0017-5749 (Linking) VI - 69 IP - 7 DP - 2020 Jul TI - Myristoleic acid produced by enterococci reduces obesity through brown adipose tissue activation. PG - 1239-1247 LID - 10.1136/gutjnl-2019-319114 [doi] AB - OBJECTIVE: Dietary fibre has beneficial effects on energy metabolism, and the majority of studies have focused on short-chain fatty acids produced by gut microbiota. Ginseng has been reported to aid in body weight management, however, its mechanism of action is not yet clear. In this study, we focused on the potential modulating effect of ginseng on gut microbiota, aiming to identify specific strains and their metabolites, especially long-chain fatty acids (LCFA), which mediate the anti-obesity effects of ginseng. DESIGN: Db/db mice were gavaged with ginseng extract (GE) and the effects of GE on gut microbiota were evaluated using 16S rDNA-based high throughput sequencing. To confirm the candidate fatty acids, untargeted metabolomics analyses of the serum and medium samples were performed. RESULTS: We demonstrated that GE can induce Enterococcus faecalis, which can produce an unsaturated LCFA, myristoleic acid (MA). Our results indicate that E. faecalis and its metabolite MA can reduce adiposity by brown adipose tissue (BAT) activation and beige fat formation. In addition, the gene of E. faecalis encoding Acyl-CoA thioesterases (ACOTs) exhibited the biosynthetic potential to synthesise MA, as knockdown (KD) of the ACOT gene by CRISPR-dCas9 significantly reduced MA production. Furthermore, exogenous treatment with KD E. faecalis could not reproduce the beneficial effects of wild type E. faecalis, which work by augmenting the circulating MA levels. CONCLUSIONS: Our results demonstrated that the gut microbiota-LCFA-BAT axis plays an important role in host metabolism, which may provide a strategic advantage for the next generation of anti-obesity drug development. CI - (c) Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Quan, Lin-Hu AU - Quan LH AD - Key Laboratory of Natural Resource of the Changbai Mountain and Functional Molecular, Ministry of Education, Agricultural College, Yanbian University, Yanji, China. FAU - Zhang, Chuanhai AU - Zhang C AD - Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. FAU - Dong, Meng AU - Dong M AD - Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. AD - Savaid Medical School, University of the Chinese Academy of Sciences, Beijing, China. FAU - Jiang, Jun AU - Jiang J AD - Key Laboratory of Natural Resource of the Changbai Mountain and Functional Molecular, Ministry of Education, Agricultural College, Yanbian University, Yanji, China. FAU - Xu, Hongde AU - Xu H AD - School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China. FAU - Yan, Chunlong AU - Yan C AD - Key Laboratory of Natural Resource of the Changbai Mountain and Functional Molecular, Ministry of Education, Agricultural College, Yanbian University, Yanji, China. FAU - Liu, Xiaomeng AU - Liu X AD - Institute of Neuroscience and Translational Medicine, College of Life Science and Agronomy, Zhoukou Normal University, Zhoukou, Henan, China. FAU - Zhou, Huiqiao AU - Zhou H AD - Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. AD - Savaid Medical School, University of the Chinese Academy of Sciences, Beijing, China. FAU - Zhang, Hanlin AU - Zhang H AD - Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. AD - Savaid Medical School, University of the Chinese Academy of Sciences, Beijing, China. FAU - Chen, Li AU - Chen L AD - Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. AD - Savaid Medical School, University of the Chinese Academy of Sciences, Beijing, China. FAU - Zhong, Fei-Liang AU - Zhong FL AD - Key Laboratory of Natural Resource of the Changbai Mountain and Functional Molecular, Ministry of Education, Agricultural College, Yanbian University, Yanji, China. FAU - Luo, Zhao-Bo AU - Luo ZB AD - Jilin Provincial Key Laboratory of Transgenic Animal and Embryo Engineering, Yanbian University, Yanji, China. FAU - Lam, Sin-Man AU - Lam SM AD - State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China. FAU - Shui, Guanghou AU - Shui G AD - State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China. FAU - Li, Donghao AU - Li D AD - Key Laboratory of Natural Resource of the Changbai Mountain and Functional Molecular, Ministry of Education, Agricultural College, Yanbian University, Yanji, China jinw@ioz.ac.cn dhli@ybu.edu.cn. FAU - Jin, Wanzhu AU - Jin W AUID- ORCID: 0000-0002-5860-2958 AD - Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China jinw@ioz.ac.cn dhli@ybu.edu.cn. AD - Savaid Medical School, University of the Chinese Academy of Sciences, Beijing, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20191119 PL - England TA - Gut JT - Gut JID - 2985108R RN - 0 (Fatty Acids, Monounsaturated) RN - 0 (Plant Extracts) RN - 0 (RNA, Ribosomal, 16S) RN - RF23WGD123 (9-tetradecenoic acid) SB - IM MH - Adipose Tissue, Brown/*metabolism MH - Animals MH - Enterococcus faecalis/*metabolism MH - Fatty Acids, Monounsaturated/*metabolism MH - Gastrointestinal Microbiome/drug effects/genetics MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Obesity/*metabolism MH - Panax MH - Plant Extracts/pharmacology MH - RNA, Ribosomal, 16S/genetics OTO - NOTNLM OT - obesity COIS- Competing interests: None declared. EDAT- 2019/11/21 06:00 MHDA- 2021/02/17 06:00 CRDT- 2019/11/21 06:00 PHST- 2019/05/18 00:00 [received] PHST- 2019/10/21 00:00 [revised] PHST- 2019/11/06 00:00 [accepted] PHST- 2019/11/21 06:00 [pubmed] PHST- 2021/02/17 06:00 [medline] PHST- 2019/11/21 06:00 [entrez] AID - gutjnl-2019-319114 [pii] AID - 10.1136/gutjnl-2019-319114 [doi] PST - ppublish SO - Gut. 2020 Jul;69(7):1239-1247. doi: 10.1136/gutjnl-2019-319114. Epub 2019 Nov 19.