Evidence map›Paper›PMID 33589625›Full record

ArticleNature communications2021

Maternal aryl hydrocarbon receptor activation protects newborns against necrotizing enterocolitis.

Peng Lu, Yukihiro Yamaguchi, William B Fulton, Sanxia Wang, Qinjie Zhou, Hongpeng Jia, Mark L Kovler, Andres Gonzalez Salazar, Maame Sampah, Thomas Prindle and 3 more

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

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed, 1 pooled it
8.7field-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

57 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.

  1. Pooled it
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  5. Necrotizing enterocolitis.Nature reviews. Disease primers · 2026
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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

13 authors at 2 institutions in 1 country.

Peng Lu *Division of Pediatric Surgery, Johns Hopkins University School of Medicine and the Johns Hopkins Children's Center, Baltimore, MD, USA. peng.lu@jhmi.edu.
Yukihiro YamaguchiDivision of Pediatric Surgery, Johns Hopkins University School of Medicine and the Johns Hopkins Children's Center, Baltimore, MD, USA.
William B FultonDivision of Pediatric Surgery, Johns Hopkins University School of Medicine and the Johns Hopkins Children's Center, Baltimore, MD, USA.
Sanxia WangDivision of Pediatric Surgery, Johns Hopkins University School of Medicine and the Johns Hopkins Children's Center, Baltimore, MD, USA.
Qinjie ZhouDivision of Pediatric Surgery, Johns Hopkins University School of Medicine and the Johns Hopkins Children's Center, Baltimore, MD, USA.
Hongpeng JiaDivision of Pediatric Surgery, Johns Hopkins University School of Medicine and the Johns Hopkins Children's Center, Baltimore, MD, USA.
Mark L KovlerDivision of Pediatric Surgery, Johns Hopkins University School of Medicine and the Johns Hopkins Children's Center, Baltimore, MD, USA.
Andres Gonzalez SalazarDivision of Pediatric Surgery, Johns Hopkins University School of Medicine and the Johns Hopkins Children's Center, Baltimore, MD, USA.ORCID 0000-0002-2672-386X
Maame SampahDivision of Pediatric Surgery, Johns Hopkins University School of Medicine and the Johns Hopkins Children's Center, Baltimore, MD, USA.ORCID 0000-0002-3065-2275
Thomas PrindleDivision of Pediatric Surgery, Johns Hopkins University School of Medicine and the Johns Hopkins Children's Center, Baltimore, MD, USA.
Peter WipfDepartment of Chemistry, University of Pittsburgh, Pittsburgh, PA, USA.
Chhinder P Sodhi *Division of Pediatric Surgery, Johns Hopkins University School of Medicine and the Johns Hopkins Children's Center, Baltimore, MD, USA.
David J HackamDivision of Pediatric Surgery, Johns Hopkins University School of Medicine and the Johns Hopkins Children's Center, Baltimore, MD, USA. Dhackam1@jhmi.edu.ORCID 0000-0001-5195-8807
Johns Hopkins University · USUniversity of Pittsburgh · US

Funding

Clinical and Laboratory Research Training for Gastrointestinal SurgeonsT32DK007713 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI DAVID J HACKAM · 1996 to 2026
$5.2M
TLR4 Signaling in the Pathogenesis of Surgical Necrotizing EnterocolitisR01GM078238 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI HACKAM, DAVID J · 2006 to 2019
$3.9M
Maternal-Fetal AHR Signaling in the Pathogenesis and Treatment of Necrotizing EnterocolitisR01DK117186 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI HACKAM, DAVID J · 2018 to 2021
$1.5M
NIDDK NIH HHS R01 DK117186NIDDK NIH HHS T32 DK007713NIGMS NIH HHS R01 GM078238
6 · The paper itself

Abstract

Necrotizing enterocolitis (NEC) is a disease of premature infants characterized by acute intestinal necrosis. Current dogma suggests that NEC develops in response to post-natal dietary and bacterial factors, and so a potential role for in utero factors in NEC remains unexplored. We now show that during pregnancy, administration of a diet rich in the aryl hydrocarbon receptor (AHR) ligand indole-3-carbinole (I3C), or of breast milk, activates AHR and prevents NEC in newborn mice by reducing Toll-like receptor 4 (TLR4) signaling in the newborn gut. Protection from NEC requires activation of AHR in the intestinal epithelium which is reduced in mouse and human NEC, and is independent of leukocyte activation. Finally, we identify an AHR ligand ("A18") that limits TLR4 signaling in mouse and human intestine, and prevents NEC in mice when administered during pregnancy. In summary, AHR signaling is critical in NEC development, and maternally-delivered, AHR-based therapies may alleviate NEC.

Indexed as

AnimalsAnimals, NewbornBasic Helix-Loop-Helix ProteinsCytochrome P-450 CYP1A1DietDisease Models, AnimalEnterocolitis, NecrotizingFemaleGene Expression RegulationHumansIndolesInfant, NewbornInfant, PrematureIntestinal MucosaLigandsMaternal ExposureAHR protein, humanAhr protein, mouseBasic Helix-Loop-Helix ProteinsCyp1a1 protein, mouseCytochrome P-450 CYP1A1indole-3-carbinolIndolesLigandsReceptors, Aryl HydrocarbonTLR4 protein, humanTlr4 protein, mouseToll-Like Receptor 4

Identifiers

PMID33589625
PMCPMC7884836
OpenAlexW3129369845

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.