Glycan Biosynthesis Ability of Gut Microbiota Increased in Primary Hypertension Patients Taking Antihypertension Medications and Potentially Promoted by Macrophage-Adenosine Monophosphate-Activated Protein Kinase

Increasing evidences suggest that the gut microbiota have their contributions to the hypertension, but the metagenomic characteristics and potential regulating mechanisms in primary hypertension patients taking antihypertension drugs are not clear yet. We carried out a metagenomic analysis in 30 pri...

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Autores principales: Shuai Zheng, Chunmei Piao, Yan Liu, Xuxia Liu, Tingting Liu, Xiaoping Zhang, Jingyuan Ren, Yulei Liu, Baoli Zhu, Jie Du
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Publicado: Frontiers Media S.A. 2021
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spelling oai:doaj.org-article:932fe24785bc4fa3b6382bac6f830af12021-11-04T06:51:45ZGlycan Biosynthesis Ability of Gut Microbiota Increased in Primary Hypertension Patients Taking Antihypertension Medications and Potentially Promoted by Macrophage-Adenosine Monophosphate-Activated Protein Kinase1664-302X10.3389/fmicb.2021.719599https://doaj.org/article/932fe24785bc4fa3b6382bac6f830af12021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmicb.2021.719599/fullhttps://doaj.org/toc/1664-302XIncreasing evidences suggest that the gut microbiota have their contributions to the hypertension, but the metagenomic characteristics and potential regulating mechanisms in primary hypertension patients taking antihypertension drugs are not clear yet. We carried out a metagenomic analysis in 30 primary hypertension patients taking antihypertension medications and eight healthy adults without any medication. We found that bacterial strains from species, such as Bacteroides fragilis, Bacteroides vulgatus, Escherichia coli, Klebsiella pneumoniae, and Streptococcus vestibularis, were highly increased in patients; and these strains were reported to generate glycan, short-chain fatty acid (SCFA) and trimethylamine (TMA) or be opportunistic pathogens. Meanwhile, Dorea longicatena, Eubacterium hallii, Clostridium leptum, Faecalibacterium prausnitzii, and some other strains were greatly decreased in the patient group. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that ortholog groups and pathways related to glycan biosynthesis and multidrug resistance were significantly increased in the patient group, and some of the hub genes related to N-glycan biosynthesis were increased in the patient group, while those related to TMA precursor metabolism and amino acid metabolism both increased and decreased in the patient group. Metabolites tested by untargeted liquid chromatography–mass spectrometry (LC-MS) proved the decrease of acetic acid, choline, betaine, and several amino acids in patients’ fecal samples. Moreover, meta-analysis of recent studies found that almost all patients were taking at least one kind of drugs that were reported to regulate adenosine monophosphate-activated protein kinase (AMPK) pathway, so we further investigated if AMPK regulated the metagenomic changes by using angiotensin II-induced mouse hypertensive model on wild-type and macrophage-specific AMPK-knockout mice. We found that the changes in E. coli and Dorea and glycan biosynthesis-related orthologs and pathways were similar in our cohort and hypertensive wild-type mice but reversed after AMPK knockout. These results suggest that the gut microbiota-derived glycan, SCFA, TMA, and some other metabolites change in medication-taking primary hypertension patients and that medications might promote gut microbiota glycan biosynthesis through activating macrophage-AMPK.Shuai ZhengShuai ZhengShuai ZhengChunmei PiaoChunmei PiaoChunmei PiaoYan LiuYan LiuYan LiuXuxia LiuXuxia LiuXuxia LiuTingting LiuTingting LiuTingting LiuXiaoping ZhangXiaoping ZhangXiaoping ZhangJingyuan RenYulei LiuBaoli ZhuBaoli ZhuJie DuJie DuJie DuFrontiers Media S.A.articlegut microbiotaprimary hypertensionmedicationmacrophageAMP-activated protein kinaseglycanMicrobiologyQR1-502ENFrontiers in Microbiology, Vol 12 (2021)
institution DOAJ
collection DOAJ
language EN
topic gut microbiota
primary hypertension
medication
macrophage
AMP-activated protein kinase
glycan
Microbiology
QR1-502
spellingShingle gut microbiota
primary hypertension
medication
macrophage
AMP-activated protein kinase
glycan
Microbiology
QR1-502
Shuai Zheng
Shuai Zheng
Shuai Zheng
Chunmei Piao
Chunmei Piao
Chunmei Piao
Yan Liu
Yan Liu
Yan Liu
Xuxia Liu
Xuxia Liu
Xuxia Liu
Tingting Liu
Tingting Liu
Tingting Liu
Xiaoping Zhang
Xiaoping Zhang
Xiaoping Zhang
Jingyuan Ren
Yulei Liu
Baoli Zhu
Baoli Zhu
Jie Du
Jie Du
Jie Du
Glycan Biosynthesis Ability of Gut Microbiota Increased in Primary Hypertension Patients Taking Antihypertension Medications and Potentially Promoted by Macrophage-Adenosine Monophosphate-Activated Protein Kinase
description Increasing evidences suggest that the gut microbiota have their contributions to the hypertension, but the metagenomic characteristics and potential regulating mechanisms in primary hypertension patients taking antihypertension drugs are not clear yet. We carried out a metagenomic analysis in 30 primary hypertension patients taking antihypertension medications and eight healthy adults without any medication. We found that bacterial strains from species, such as Bacteroides fragilis, Bacteroides vulgatus, Escherichia coli, Klebsiella pneumoniae, and Streptococcus vestibularis, were highly increased in patients; and these strains were reported to generate glycan, short-chain fatty acid (SCFA) and trimethylamine (TMA) or be opportunistic pathogens. Meanwhile, Dorea longicatena, Eubacterium hallii, Clostridium leptum, Faecalibacterium prausnitzii, and some other strains were greatly decreased in the patient group. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that ortholog groups and pathways related to glycan biosynthesis and multidrug resistance were significantly increased in the patient group, and some of the hub genes related to N-glycan biosynthesis were increased in the patient group, while those related to TMA precursor metabolism and amino acid metabolism both increased and decreased in the patient group. Metabolites tested by untargeted liquid chromatography–mass spectrometry (LC-MS) proved the decrease of acetic acid, choline, betaine, and several amino acids in patients’ fecal samples. Moreover, meta-analysis of recent studies found that almost all patients were taking at least one kind of drugs that were reported to regulate adenosine monophosphate-activated protein kinase (AMPK) pathway, so we further investigated if AMPK regulated the metagenomic changes by using angiotensin II-induced mouse hypertensive model on wild-type and macrophage-specific AMPK-knockout mice. We found that the changes in E. coli and Dorea and glycan biosynthesis-related orthologs and pathways were similar in our cohort and hypertensive wild-type mice but reversed after AMPK knockout. These results suggest that the gut microbiota-derived glycan, SCFA, TMA, and some other metabolites change in medication-taking primary hypertension patients and that medications might promote gut microbiota glycan biosynthesis through activating macrophage-AMPK.
format article
author Shuai Zheng
Shuai Zheng
Shuai Zheng
Chunmei Piao
Chunmei Piao
Chunmei Piao
Yan Liu
Yan Liu
Yan Liu
Xuxia Liu
Xuxia Liu
Xuxia Liu
Tingting Liu
Tingting Liu
Tingting Liu
Xiaoping Zhang
Xiaoping Zhang
Xiaoping Zhang
Jingyuan Ren
Yulei Liu
Baoli Zhu
Baoli Zhu
Jie Du
Jie Du
Jie Du
author_facet Shuai Zheng
Shuai Zheng
Shuai Zheng
Chunmei Piao
Chunmei Piao
Chunmei Piao
Yan Liu
Yan Liu
Yan Liu
Xuxia Liu
Xuxia Liu
Xuxia Liu
Tingting Liu
Tingting Liu
Tingting Liu
Xiaoping Zhang
Xiaoping Zhang
Xiaoping Zhang
Jingyuan Ren
Yulei Liu
Baoli Zhu
Baoli Zhu
Jie Du
Jie Du
Jie Du
author_sort Shuai Zheng
title Glycan Biosynthesis Ability of Gut Microbiota Increased in Primary Hypertension Patients Taking Antihypertension Medications and Potentially Promoted by Macrophage-Adenosine Monophosphate-Activated Protein Kinase
title_short Glycan Biosynthesis Ability of Gut Microbiota Increased in Primary Hypertension Patients Taking Antihypertension Medications and Potentially Promoted by Macrophage-Adenosine Monophosphate-Activated Protein Kinase
title_full Glycan Biosynthesis Ability of Gut Microbiota Increased in Primary Hypertension Patients Taking Antihypertension Medications and Potentially Promoted by Macrophage-Adenosine Monophosphate-Activated Protein Kinase
title_fullStr Glycan Biosynthesis Ability of Gut Microbiota Increased in Primary Hypertension Patients Taking Antihypertension Medications and Potentially Promoted by Macrophage-Adenosine Monophosphate-Activated Protein Kinase
title_full_unstemmed Glycan Biosynthesis Ability of Gut Microbiota Increased in Primary Hypertension Patients Taking Antihypertension Medications and Potentially Promoted by Macrophage-Adenosine Monophosphate-Activated Protein Kinase
title_sort glycan biosynthesis ability of gut microbiota increased in primary hypertension patients taking antihypertension medications and potentially promoted by macrophage-adenosine monophosphate-activated protein kinase
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/932fe24785bc4fa3b6382bac6f830af1
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