Evidence map›Paper›PMID 32142679›Full record

ArticleCell2020

A Cardiovascular Disease-Linked Gut Microbial Metabolite Acts via Adrenergic Receptors.

Ina Nemet, Prasenjit Prasad Saha, Nilaksh Gupta, Weifei Zhu, Kymberleigh A Romano, Sarah M Skye, Tomas Cajka, Maradumane L Mohan, Lin Li, Yuping Wu and 9 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 485 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
485citing papers in PubMed, 6 pooled it
33.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

485 citing papers in PubMed, 6 syntheses or guidelines pooled it, 709 citations in OpenAlex.

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425 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 7 institutions in 1 country.

Ina NemetDepartment of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA; Center for Microbiome & Human Health, Cleveland Clinic, Cleveland, OH 44106, USA.
Prasenjit Prasad SahaDepartment of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA; Center for Microbiome & Human Health, Cleveland Clinic, Cleveland, OH 44106, USA.
Nilaksh GuptaDepartment of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA; Center for Microbiome & Human Health, Cleveland Clinic, Cleveland, OH 44106, USA.
Weifei ZhuDepartment of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA; Center for Microbiome & Human Health, Cleveland Clinic, Cleveland, OH 44106, USA.
Kymberleigh A RomanoDepartment of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA; Center for Microbiome & Human Health, Cleveland Clinic, Cleveland, OH 44106, USA.
Sarah M SkyeDepartment of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA; Center for Microbiome & Human Health, Cleveland Clinic, Cleveland, OH 44106, USA.
Tomas CajkaWest Coast Metabolomics Center, University of California, Davis, Davis, CA 95616, USA.
Maradumane L MohanDepartment of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA.
Lin LiDepartment of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA; Center for Microbiome & Human Health, Cleveland Clinic, Cleveland, OH 44106, USA.
Yuping WuDepartment of Mathematics, Cleveland State University, Cleveland, OH 44115, USA.
Masanori FunabashiDepartment of Bioengineering and ChEM-H, Stanford University, Stanford, CA 94305, USA.
Amanda E Ramer-TaitDepartment of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE 68588, USA.
Sathyamangla Venkata Naga PrasadDepartment of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA.
Oliver FiehnWest Coast Metabolomics Center, University of California, Davis, Davis, CA 95616, USA.
Federico E ReyDepartment of Bacteriology, University of Wisconsin-Madison, Madison, WI 53706, USA.
W H Wilson TangDepartment of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA; Center for Microbiome & Human Health, Cleveland Clinic, Cleveland, OH 44106, USA; Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH 44106, USA.
Michael A FischbachDepartment of Bioengineering and ChEM-H, Stanford University, Stanford, CA 94305, USA.
Joseph A DiDonatoDepartment of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA; Center for Microbiome & Human Health, Cleveland Clinic, Cleveland, OH 44106, USA.
Stanley L HazenDepartment of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA; Center for Microbiome & Human Health, Cleveland Clinic, Cleveland, OH 44106, USA; Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH 44106, USA. Electronic address: hazens@ccf.org.
Cleveland Clinic · USCleveland Clinic Lerner College of Medicine · USStanford University · USUniversity of California, Davis · USCleveland State University · USUniversity of Nebraska–Lincoln · USUniversity of Wisconsin–Madison · US

Funding

Project 3: Microbiota generated aryl sulfates and secondary bile acids in cardiometabolic diseaseP01HL147823 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI Stanley L Hazen · 2019 to 2026
$17.0M
Gut Flora Metabolism of Dietary Phosphatidylcholine and CVDR01HL103866 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI HAZEN, STANLEY L · 2010 to 2023
$10.8M
Diet, Gut Microbiota, and Heart FailureR01HL126827 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI HAZEN, STANLEY L, TANG, WAI HONG WILSON · 2016 to 2019
$3.1M
CWRU- Cardiovascular Research Training ProgramT32HL134622 · NHLBI · CASE WESTERN RESERVE UNIVERSITY · PI JAIN, MUKESH KUMAR, PROWELLER, AARON · 2017 to 2021
$1.9M
AB/SCIEX QTrap 6500 Mass Spectrometer Metabolic profiling systemS10OD016346 · OD · CLEVELAND CLINIC LERNER COM-CWRU · PI DIDONATO, JOSEPH · 2014 to 2014
$600k
NHLBI NIH HHS P01 HL147823NHLBI NIH HHS R01 HL103866NHLBI NIH HHS R01 HL126827NHLBI NIH HHS T32 HL134622NIH HHS S10 OD016346
6 · The paper itself

Abstract

Using untargeted metabolomics (n = 1,162 subjects), the plasma metabolite (m/z = 265.1188) phenylacetylglutamine (PAGln) was discovered and then shown in an independent cohort (n = 4,000 subjects) to be associated with cardiovascular disease (CVD) and incident major adverse cardiovascular events (myocardial infarction, stroke, or death). A gut microbiota-derived metabolite, PAGln, was shown to enhance platelet activation-related phenotypes and thrombosis potential in whole blood, isolated platelets, and animal models of arterial injury. Functional and genetic engineering studies with human commensals, coupled with microbial colonization of germ-free mice, showed the microbial porA gene facilitates dietary phenylalanine conversion into phenylacetic acid, with subsequent host generation of PAGln and phenylacetylglycine (PAGly) fostering platelet responsiveness and thrombosis potential. Both gain- and loss-of-function studies employing genetic and pharmacological tools reveal PAGln mediates cellular events through G-protein coupled receptors, including α2A, α2B, and β2-adrenergic receptors. PAGln thus represents a new CVD-promoting gut microbiota-dependent metabolite that signals via adrenergic receptors.

Indexed as

AnimalsArteriesBacterial ProteinsBlood PlateletsCardiovascular DiseasesDeath, Sudden, CardiacGastrointestinal MicrobiomeGlutamineHumansMaleMetabolomeMetabolomicsMiceMyocardial InfarctionPlatelet ActivationReceptors, Adrenergic, alphaBacterial ProteinsGlutaminephenylacetylglutamineReceptors, Adrenergic, alphaReceptors, Adrenergic, betaadrenergic receptorscardiovascular diseaseGPCRgut microbemetabolomicsthrombosis

Identifiers

PMID32142679
PMCPMC7402401
OpenAlexW3009682272

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.