Evidence map›Paper›PMID 33436815›Full record

ArticleScientific reports2021

Inhibition of microbiota-dependent TMAO production attenuates chronic kidney disease in mice.

Wenchao Zhang, Aika Miikeda, Jonathan Zuckerman, Xun Jia, Sarada Charugundla, Zhiqiang Zhou, Karolina Elżbieta Kaczor-Urbanowicz, Clara Magyar, Fangfei Guo, Zeneng Wang and 5 more

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

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
94citing papers in PubMed, 3 pooled it
8.5field-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

94 citing papers in PubMed, 3 syntheses or guidelines pooled it, 142 citations in OpenAlex.

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

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

15 authors at 5 institutions in 2 countries.

Wenchao ZhangThe Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China.
Aika MiikedaDivision of Cardiology, Department of Medicine, University of California, 10833 Le Conte Avenue, A2-237 CHS, Los Angeles, CA, 90095-1679, USA.
Jonathan ZuckermanDepartment of Pathology and Laboratory, University of California, Los Angeles, CA, 90095, USA.
Xun JiaDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Sarada CharugundlaDivision of Cardiology, Department of Medicine, University of California, 10833 Le Conte Avenue, A2-237 CHS, Los Angeles, CA, 90095-1679, USA.
Zhiqiang ZhouDivision of Cardiology, Department of Medicine, University of California, 10833 Le Conte Avenue, A2-237 CHS, Los Angeles, CA, 90095-1679, USA.
Karolina Elżbieta Kaczor-UrbanowiczDivision of Oral Biology and Medicine, Center for the Health Sciences, UCLA School of Dentistry, Center for Oral and Head/Neck Oncology Research, UCLA Section of Oral Biology, University of California, 10833 Le Conte Ave, Box 951668, Los Angeles, CA, 90095, USA.
Clara MagyarTranslational Pathology Core Laboratory, University of California, Los Angeles, CA, 90095, USA.
Fangfei GuoDivision of Cardiology, Department of Medicine, University of California, 10833 Le Conte Avenue, A2-237 CHS, Los Angeles, CA, 90095-1679, USA.
Zeneng WangDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Matteo PellegriniMolecular, Cell, & Developmental Biology, University of California, Los Angeles, CA, 90095, USA.
Stanley L HazenDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Susanne B NicholasDepartment of Medicine/Division of Nephrology, University of California, Los Angeles, CA, 90095, USA.
Aldons J LusisDivision of Cardiology, Department of Medicine, University of California, 10833 Le Conte Avenue, A2-237 CHS, Los Angeles, CA, 90095-1679, USA.
Diana M ShihDivision of Cardiology, Department of Medicine, University of California, 10833 Le Conte Avenue, A2-237 CHS, Los Angeles, CA, 90095-1679, USA. dshih@mednet.ucla.edu.
University of California, Los Angeles · USCleveland Clinic Lerner College of Medicine · USCleveland Clinic · USOklahoma State University Center for Health Sciences · USShandong University · CN

Funding

Project 3: Microbiota generated aryl sulfates and secondary bile acids in cardiometabolic diseaseP01HL147823 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI MICHAEL ANDREW FISCHBACH · 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
Systems genetics approach to inflammatory mechanisms in atherosclerosisR01HL147883 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LUSIS, ALDONS JAKE · 2019 to 2022
$3.0M
Gut microbiota and metabolite interactions in atherosclerosisR01HL144651 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LUSIS, ALDONS JAKE, REY, FEDERICO E · 2019 to 2022
$2.6M
Biological Mechanisms through which TMAO Promotes AtherosclerosisR01HL148110 · NHLBI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ALLAYEE, HOOMAN, SHIH, DIANA MOUHAN · 2020 to 2023
$2.5M
Microbial Trimethylamine Lyases and AtherosclerosisR01HL130819 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI WANG, ZENENG · 2016 to 2019
$1.7M
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 HL130819NHLBI NIH HHS R01 HL144651NHLBI NIH HHS R01 HL147883NHLBI NIH HHS R01 HL148110
6 · The paper itself

Abstract

Patients with chronic kidney disease (CKD) have elevated circulating levels of trimethylamine N-oxide (TMAO), a metabolite derived from gut microbes and associated with cardiovascular diseases. High circulating levels of TMAO and its dietary precursor, choline, predict increased risk for development of CKD in apparently healthy subjects, and studies in mice fed TMAO or choline suggest that TMAO can contribute to kidney impairment and renal fibrosis. Here we examined the interactions between TMAO, kidney disease, and cardiovascular disease in mouse models. We observed that while female hyperlipidemic apoE KO mice fed a 0.2% adenine diet for 14 weeks developed CKD with elevated plasma levels of TMAO, provision of a non-lethal inhibitor of gut microbial trimethylamine (TMA) production, iodomethylcholine (IMC), significantly reduced multiple markers of renal injury (plasma creatinine, cystatin C, FGF23, and TMAO), reduced histopathologic evidence of fibrosis, and markedly attenuated development of microalbuminuria. In addition, while the adenine-induced CKD model significantly increased heart weight, a surrogate marker for myocardial hypertrophy, this was largely prevented by IMC supplementation. Surprisingly, adenine feeding did not increase atherosclerosis and significantly decreased the expression of inflammatory genes in the aorta compared to the control groups, effects unrelated to TMAO levels. Our data demonstrate that inhibition of TMAO production attenuated CKD development and cardiac hypertrophy in mice, suggesting that TMAO reduction may be a novel strategy in treating CKD and its cardiovascular disease complications.

Indexed as

AdenineAlbuminuriaAnimalsCardiomegalyCholineDisease Models, AnimalFemaleFibroblast Growth Factor-23FibrosisGastrointestinal MicrobiomeKidneyMethylaminesMiceRenal Insufficiency, ChronicAdenineCholineFgf23 protein, mouseFibroblast Growth Factor-23Methylaminesmethylcholinetrimethyloxamine

Identifiers

PMID33436815
PMCPMC7804188
OpenAlexW3120506626

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Registered trials

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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 OpenQuestion graph.