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

Shuai Zheng; Chunmei Piao; Yan Liu; Xuxia Liu; Tingting Liu; Xiaoping Zhang; Jingyuan Ren; Yulei Liu; Baoli Zhu; Jie Du

doi:10.3389/fmicb.2021.719599

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

Front Microbiol. 2021 Nov 4:12:719599. doi: 10.3389/fmicb.2021.719599. eCollection 2021.

Authors

Shuai Zheng^{1

2

3}, Chunmei Piao^{1

2

3}, Yan Liu^{1

2

3}, Xuxia Liu^{1

2

3}, Tingting Liu^{1

2

3}, Xiaoping Zhang^{1

2

3}, Jingyuan Ren⁴, Yulei Liu⁵, Baoli Zhu^{6

7}, Jie Du^{1

2

3}

Affiliations

¹ Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
² Beijing Collaborative Innovation Centre for Cardiovascular Disorders, Beijing, China.
³ The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China.
⁴ Department of Hypertension, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
⁵ Department of Clinic Laboratory, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
⁶ CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
⁷ Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

Abstract

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.

Keywords: AMP-activated protein kinase; glycan; gut microbiota; macrophage; medication; primary hypertension.