Evidence map›Paper›PMID 39738016›Full record

ArticleNature communications2024

Alcohol-induced gut microbial reorganization and associated overproduction of phenylacetylglutamine promotes cardiovascular disease.

Zhen Li, Min Gu, Aline Zaparte, Xiaoming Fu, Kala Mahen, Marko Mrdjen, Xinmin S Li, Zhihong Yang, Jing Ma, Themis Thoudam and 17 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
–field-weighted citation impact
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

12 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Review
  11. Alcohol exposure alters the diversity and composition of oral microbiome.Frontiers in cellular and infection microbiology · 2025
    Article
  12. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

27 authors.

Zhen LiDepartment of Cardiac Surgery, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Min GuSection of Pulmonary/Critical Care and Allergy/Immunology, Department of Medicine, Louisiana State University Health Science Center, New Orleans, LA, USA.
Aline ZaparteSection of Pulmonary/Critical Care and Allergy/Immunology, Department of Medicine, Louisiana State University Health Science Center, New Orleans, LA, USA.ORCID 0000-0003-4069-3676
Xiaoming FuDepartment of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Kala MahenDepartment of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Marko MrdjenDepartment of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Xinmin S LiDepartment of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.ORCID 0000-0003-4946-4271
Zhihong YangDivision of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.ORCID 0000-0001-6199-3956
Jing MaDivision of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Themis ThoudamDivision of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.ORCID 0000-0002-3845-2964
Kristina ChandlerDivision of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Maggie HeslerDivision of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Laura HeathersDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.ORCID 0009-0008-1097-2678
Kiersten GorseDepartment of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Thanh Trung VanDepartment of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
David WongIntegrative Biology and Physiology, University of California, Los Angeles, CA, USA.ORCID 0000-0002-0712-153X
Aaron M GibsonThe Heart Institute, Division of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Zeneng WangDepartment of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.ORCID 0000-0002-6455-8228
Christopher M TaylorComprehensive Alcohol Research Center, School of Medicine, Louisiana State University Health Science Center, New Orleans, LA, USA.ORCID 0000-0002-7983-5275
Pearl QuijadaIntegrative Biology and Physiology, University of California, Los Angeles, CA, USA.ORCID 0000-0003-2477-2374
Catherine A MakarewichThe Heart Institute, Division of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.ORCID 0000-0001-6907-4401
Stanley L HazenDepartment of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.ORCID 0000-0001-7124-6639
Suthat LiangpunsakulDivision of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
J Mark BrownDepartment of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.ORCID 0000-0003-2708-7487
David J LeferDepartment of Cardiac Surgery, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.ORCID 0000-0003-2293-7278
David A WelshSection of Pulmonary/Critical Care and Allergy/Immunology, Department of Medicine, Louisiana State University Health Science Center, New Orleans, LA, USA.ORCID 0000-0002-0008-6161
Thomas E SharpDepartment of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA. tesharp@usf.edu.ORCID 0000-0001-8706-9825

Funding

Tracking & Evaluation CoreU54GM104940 · NIGMS · LSU PENNINGTON BIOMEDICAL RESEARCH CTR · PI Peter Todd Katzmarzyk · 2012 to 2026
$69.1M
STABILITY' (symptomatic review during biologic therapy) Review in Inflammatory Bowel DiseaseP20GM103424 · NIGMS · LOUISIANA STATE UNIV A&M COL BATON ROUGE · PI VLADIMIR N CHOULJENKO · 2012 to 2026
$57.4M
Translational Research/Education ComponentP60AA009803 · NIAAA · LSU HEALTH SCIENCES CENTER · PI PATRICIA E. MOLINA · 2004 to 2026
$42.6M
Project Two - Exercise Training Decreases Alcohol Drinking by an FGF21-Dependent MechanismP50AA024333 · NIAAA · CLEVELAND CLINIC LERNER COM-CWRU · PI Srinivasan Dasarathy · 2016 to 2026
$19.6M
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
Vascular Biology Training GrantT32HL069766 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LUSIS, ALDONS JAKE · 2002 to 2022
$7.4M
Muscle Cell Biology, Pathophysiology, and TherapeuticsT32AR065972 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Rachelle Hope Crosbie, THOMAS A. RANDO · 2016 to 2026
$3.9M
UCSD PRIDE Faculty Development Program in Cardiovascular SciencesR25HL145817 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Robert Scott Ross, Joann Trejo · 2019 to 2026
$3.3M
UCLA LIFT-UP (Leveraging Institutional support For Talented, Upcoming Physicians and/or Scientists)U24DK132746 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI OBIDIUGWU KENRIK DURU, CAROL M MANGIONE · 2022 to 2026
$3.2M
Roles of Endothelial and Smooth Muscle KATP Channels in Myocardial Ischemic InjuryR01HL146514 · NHLBI · LSU HEALTH SCIENCES CENTER · PI COETZEE, WILLIAM A, LEFER, DAVID JOSEPH · 2020 to 2023
$3.0M
Metaorganismal Endocrinology in Cardiometabolic DiseaseR01DK130227 · NIDDK · CLEVELAND CLINIC LERNER COM-CWRU · PI Jonathan Mark Brown · 2021 to 2026
$2.8M
BLRD VA I01 BX006202CSRD VA I01 CX000361National Science Foundation (NSF) NSF 2018936NHLBI NIH HHS P01 HL147823NHLBI NIH HHS R01 HL103866NHLBI NIH HHS R01 HL146098NHLBI NIH HHS R01 HL146514NHLBI NIH HHS R01 HL151398NHLBI NIH HHS R01 HL160569NHLBI NIH HHS R01 HL167831NHLBI NIH HHS R01 HL171221NHLBI NIH HHS R25 HL145817NHLBI NIH HHS T32 HL069766NIAAA NIH HHS P50 AA024333NIAAA NIH HHS P60 AA009803NIAAA NIH HHS R01 AA029984NIAAA NIH HHS R01 AA030312NIAAA NIH HHS R21 AA027199NIAAA NIH HHS U01 AA026917NIAAA NIH HHS UH2 AA026226NIAAA NIH HHS UH3 AA026903NIAMS NIH HHS T32 AR065972NIDDK NIH HHS R01 DK120679NIDDK NIH HHS R01 DK130227NIDDK NIH HHS U24 DK132746NIGMS NIH HHS P20 GM103424NIGMS NIH HHS U54 GM104940NINDS NIH HHS RF1 NS133812U.S. Department of Defense (United States Department of Defense) KC2210163U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) HL160569U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) HL171221U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) U24 DK1132746U.S. Department of Health & Human Services | NIH | National Institute on Alcohol Abuse and Alcoholism (NIAAA) R01AA030312
6 · The paper itself

Abstract

The mechanism(s) underlying gut microbial metabolite (GMM) contribution towards alcohol-mediated cardiovascular disease (CVD) is unknown. Herein we observe elevation in circulating phenylacetylglutamine (PAGln), a known CVD-associated GMM, in individuals living with alcohol use disorder. In a male murine binge-on-chronic alcohol model, we confirm gut microbial reorganization, elevation in PAGln levels, and the presence of cardiovascular pathophysiology. Fecal microbiota transplantation from pair-/alcohol-fed mice into naïve male mice demonstrates the transmissibility of PAGln production and the CVD phenotype. Independent of alcohol exposure, pharmacological-mediated increases in PAGln elicits direct cardiac and vascular dysfunction. PAGln induced hypercontractility and altered calcium cycling in isolated cardiomyocytes providing evidence of improper relaxation which corresponds to elevated filling pressures observed in vivo. Furthermore, PAGln directly induces vascular endothelial cell activation through induction of oxidative stress leading to endothelial cell dysfunction. We thus reveal that the alcohol-induced microbial reorganization and resultant GMM elevation, specifically PAGln, directly contributes to CVD.

Indexed as

Cardiovascular DiseasesGastrointestinal MicrobiomeGlutamineAlcoholismAnimalsDisease Models, AnimalEndothelial CellsEthanolFecal Microbiota TransplantationFemaleGlutamatesHumansMaleMiceMice, Inbred C57BLMiddle AgedEthanolGlutamatesGlutaminephenylacetylglutamine

Identifiers

PMID39738016
PMCPMC11685538

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.