Berberine attenuates choline-induced atherosclerosis by inhibiting trimethylamine and trimethylamine-N-oxide production via manipulating the gut microbiome

Abstract Trimethylamine-N-oxide (TMAO), a derivative from the gut microbiota metabolite trimethylamine (TMA), has been identified to be an independent risk factor for promoting atherosclerosis. Evidences suggest that berberine (BBR) could be used to treat obesity, diabetes and atherosclerosis, howev...

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Autores principales: Xingxing Li, Chunyan Su, Zhibo Jiang, Yuxin Yang, Yue Zhang, Mengxia Yang, Xiumin Zhang, Yu Du, Jin Zhang, Li Wang, Jiandong Jiang, Bin Hong
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/0f86d6cd8abd41db8c4a1703821317e7
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spelling oai:doaj.org-article:0f86d6cd8abd41db8c4a1703821317e72021-12-02T14:26:17ZBerberine attenuates choline-induced atherosclerosis by inhibiting trimethylamine and trimethylamine-N-oxide production via manipulating the gut microbiome10.1038/s41522-021-00205-82055-5008https://doaj.org/article/0f86d6cd8abd41db8c4a1703821317e72021-04-01T00:00:00Zhttps://doi.org/10.1038/s41522-021-00205-8https://doaj.org/toc/2055-5008Abstract Trimethylamine-N-oxide (TMAO), a derivative from the gut microbiota metabolite trimethylamine (TMA), has been identified to be an independent risk factor for promoting atherosclerosis. Evidences suggest that berberine (BBR) could be used to treat obesity, diabetes and atherosclerosis, however, its mechanism is not clear mainly because of its poor oral bioavailability. Here, we show that BBR attenuated TMA/TMAO production in the C57BL/6J and ApoE KO mice fed with choline-supplemented chow diet, and mitigated atherosclerotic lesion areas in ApoE KO mice. Inhibition of TMA/TMAO production by BBR-modulated gut microbiota was proved by a single-dose administration of d9-choline in vivo. Metagenomic analysis of cecal contents demonstrated that BBR altered gut microbiota composition, microbiome functionality, and cutC/cntA gene abundance. Furthermore, BBR was shown to inhibit choline-to-TMA conversion in TMA-producing bacteria in vitro and in gut microbial consortium from fecal samples of choline-fed mice and human volunteers, and the result was confirmed by transplantation of TMA-producing bacteria in mice. These results offer new insights into the mechanisms responsible for the anti-atherosclerosis effects of BBR, which inhibits commensal microbial TMA production via gut microbiota remodeling.Xingxing LiChunyan SuZhibo JiangYuxin YangYue ZhangMengxia YangXiumin ZhangYu DuJin ZhangLi WangJiandong JiangBin HongNature PortfolioarticleMicrobial ecologyQR100-130ENnpj Biofilms and Microbiomes, Vol 7, Iss 1, Pp 1-14 (2021)
institution DOAJ
collection DOAJ
language EN
topic Microbial ecology
QR100-130
spellingShingle Microbial ecology
QR100-130
Xingxing Li
Chunyan Su
Zhibo Jiang
Yuxin Yang
Yue Zhang
Mengxia Yang
Xiumin Zhang
Yu Du
Jin Zhang
Li Wang
Jiandong Jiang
Bin Hong
Berberine attenuates choline-induced atherosclerosis by inhibiting trimethylamine and trimethylamine-N-oxide production via manipulating the gut microbiome
description Abstract Trimethylamine-N-oxide (TMAO), a derivative from the gut microbiota metabolite trimethylamine (TMA), has been identified to be an independent risk factor for promoting atherosclerosis. Evidences suggest that berberine (BBR) could be used to treat obesity, diabetes and atherosclerosis, however, its mechanism is not clear mainly because of its poor oral bioavailability. Here, we show that BBR attenuated TMA/TMAO production in the C57BL/6J and ApoE KO mice fed with choline-supplemented chow diet, and mitigated atherosclerotic lesion areas in ApoE KO mice. Inhibition of TMA/TMAO production by BBR-modulated gut microbiota was proved by a single-dose administration of d9-choline in vivo. Metagenomic analysis of cecal contents demonstrated that BBR altered gut microbiota composition, microbiome functionality, and cutC/cntA gene abundance. Furthermore, BBR was shown to inhibit choline-to-TMA conversion in TMA-producing bacteria in vitro and in gut microbial consortium from fecal samples of choline-fed mice and human volunteers, and the result was confirmed by transplantation of TMA-producing bacteria in mice. These results offer new insights into the mechanisms responsible for the anti-atherosclerosis effects of BBR, which inhibits commensal microbial TMA production via gut microbiota remodeling.
format article
author Xingxing Li
Chunyan Su
Zhibo Jiang
Yuxin Yang
Yue Zhang
Mengxia Yang
Xiumin Zhang
Yu Du
Jin Zhang
Li Wang
Jiandong Jiang
Bin Hong
author_facet Xingxing Li
Chunyan Su
Zhibo Jiang
Yuxin Yang
Yue Zhang
Mengxia Yang
Xiumin Zhang
Yu Du
Jin Zhang
Li Wang
Jiandong Jiang
Bin Hong
author_sort Xingxing Li
title Berberine attenuates choline-induced atherosclerosis by inhibiting trimethylamine and trimethylamine-N-oxide production via manipulating the gut microbiome
title_short Berberine attenuates choline-induced atherosclerosis by inhibiting trimethylamine and trimethylamine-N-oxide production via manipulating the gut microbiome
title_full Berberine attenuates choline-induced atherosclerosis by inhibiting trimethylamine and trimethylamine-N-oxide production via manipulating the gut microbiome
title_fullStr Berberine attenuates choline-induced atherosclerosis by inhibiting trimethylamine and trimethylamine-N-oxide production via manipulating the gut microbiome
title_full_unstemmed Berberine attenuates choline-induced atherosclerosis by inhibiting trimethylamine and trimethylamine-N-oxide production via manipulating the gut microbiome
title_sort berberine attenuates choline-induced atherosclerosis by inhibiting trimethylamine and trimethylamine-n-oxide production via manipulating the gut microbiome
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/0f86d6cd8abd41db8c4a1703821317e7
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AT chunyansu berberineattenuatescholineinducedatherosclerosisbyinhibitingtrimethylamineandtrimethylaminenoxideproductionviamanipulatingthegutmicrobiome
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