Evidence map›Paper›PMID 32544245›Full record

ArticleToxicological sciences : an official journal of the Society of Toxicology2020

Gut Microbiome Critically Impacts PCB-induced Changes in Metabolic Fingerprints and the Hepatic Transcriptome in Mice.

Joe Jongpyo Lim, Xueshu Li, Hans-Joachim Lehmler, Dongfang Wang, Haiwei Gu, Julia Yue Cui

Open access · bronzeAbstract read
In one paragraph

Article in Toxicological sciences : an official journal of the Society of Toxicology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

27 citing papers in PubMed, 41 citations in OpenAlex.

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  16. Gene×environment interactions in autism spectrum disorders.Current topics in developmental biology · 2023
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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

6 authors at 3 institutions in 1 country.

Joe Jongpyo LimDepartment of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington 98195.
Xueshu LiDepartment of Occupational and Environmental Health, University of Iowa, Iowa City, Iowa 52242; and.
Hans-Joachim LehmlerDepartment of Occupational and Environmental Health, University of Iowa, Iowa City, Iowa 52242; and.
Dongfang WangArizona Metabolomics Laboratory, School of Nutrition and Health Promotion, College of Health Solutions, Arizona State University, Scottsdale, Arizona 85259.
Haiwei GuArizona Metabolomics Laboratory, School of Nutrition and Health Promotion, College of Health Solutions, Arizona State University, Scottsdale, Arizona 85259.
Julia Yue CuiDepartment of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington 98195.
Arizona State University · USUniversity of Iowa · USUniversity of Washington · US

Funding

Training CoreP42ES013661 · NIEHS · UNIVERSITY OF IOWA · PI Rachel Frances Marek · 2006 to 2026
$60.3M
XENOBIOTIC BIOTRANSFORMATION AND DISPOSITIONP30ES007033 · NIEHS · UNIVERSITY OF WASHINGTON · PI Sheela Sathyanarayana · 1995 to 2026
$42.5M
Pulmonary Toxicology Facility CoreP30ES005605 · NIEHS · UNIVERSITY OF IOWA · PI Jong Sung Kim · 1990 to 2026
$40.5M
Environmetal Pathology/Toxicology Training ProgramT32ES007032 · NIEHS · UNIVERSITY OF WASHINGTON · PI FAUSTMAN, ELAINE M, ROSENFELD, MICHAEL E · 1985 to 2023
$10.7M
Mechanisms of Brain Dysmorphology in MN1 C-Terminal Truncation Syndrome, a Novel Intellectual Developmental Disability Disorder P50HD103524 · NICHD · UNIVERSITY OF WASHINGTON · PI Sandra E Juul · 2020 to 2026
$9.9M
Developmental PBDE exposure, gut microbiome, and diabetesR01ES030197 · NIEHS · UNIVERSITY OF WASHINGTON · PI Julia Yue Cui, Haiwei Gu · 2019 to 2026
$5.0M
PCB-mediated dysbiosis of the gut microbiome: A missing link in PCB-mediated neurodevelopmental disorders?R01ES031098 · NIEHS · UNIVERSITY OF IOWA · PI CUI, JULIA YUE, LEHMLER, HANS-JOACHIM · 2020 to 2024
$3.1M
Epigenetic Regulation of Drug Metabolism by Developmental Exposure to PBDEsR01ES025708 · NIEHS · UNIVERSITY OF WASHINGTON · PI CUI, JULIA YUE · 2015 to 2019
$1.7M
Developmental Regulation of Drug Metabolism by Targeting the Gut MicrobiomeR01GM111381 · NIGMS · UNIVERSITY OF WASHINGTON · PI CUI, JULIA YUE · 2014 to 2018
$1.5M
NICHD NIH HHS P50 HD103524NIEHS NIH HHS P30 ES005605NIEHS NIH HHS P30 ES007033NIEHS NIH HHS P42 ES013661NIEHS NIH HHS R01 ES025708NIEHS NIH HHS R01 ES030197NIEHS NIH HHS R01 ES031098NIEHS NIH HHS T32 ES007032NIGMS NIH HHS R01 GM111381
6 · The paper itself

Abstract

Polychlorinated biphenyls (PCBs) are ubiquitously detected and have been linked to metabolic diseases. Gut microbiome is recognized as a critical regulator of disease susceptibility; however, little is known how PCBs and gut microbiome interact to modulate hepatic xenobiotic and intermediary metabolism. We hypothesized the gut microbiome regulates PCB-mediated changes in the metabolic fingerprints and hepatic transcriptome. Ninety-day-old female conventional and germ-free mice were orally exposed to the Fox River Mixture (synthetic PCB mixture, 6 or 30 mg/kg) or corn oil (vehicle control, 10 ml/kg), once daily for 3 consecutive days. RNA-seq was conducted in liver, and endogenous metabolites were measured in liver and serum by LC-MS. Prototypical target genes of aryl hydrocarbon receptor, pregnane X receptor, and constitutive androstane receptor were more readily upregulated by PCBs in conventional conditions, indicating PCBs, to the hepatic transcriptome, act partly through the gut microbiome. In a gut microbiome-dependent manner, xenobiotic, and steroid metabolism pathways were upregulated, whereas response to misfolded proteins-related pathways was downregulated by PCBs. At the high PCB dose, NADP, and arginine appear to interact with drug-metabolizing enzymes (ie, Cyp1-3 family), which are highly correlated with Ruminiclostridium and Roseburia, providing a novel explanation of gut-liver interaction from PCB-exposure. Utilizing the Library of Integrated Network-based Cellular Signatures L1000 database, therapeutics targeting anti-inflammatory and endoplasmic reticulum stress pathways are predicted to be remedies that can mitigate PCB toxicity. Our findings demonstrate that habitation of the gut microbiota drives PCB-mediated hepatic responses. Our study adds knowledge of physiological response differences from PCB exposure and considerations for further investigations for gut microbiome-dependent therapeutics.

Indexed as

Gastrointestinal MicrobiomePolychlorinated BiphenylsAnimalsFemaleLiverMiceTranscriptomePolychlorinated Biphenylsbioinformaticsbiotransformationcytochrome P450environmentalenvironmental chemicalsexposurehepatotoxicitymetabolomicsmolecular mechanismsRNA-seqtoxicogenomics

Identifiers

PMID32544245
PMCPMC7553702
OpenAlexW3034666419

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.