Evidence map›Paper›PMID 34550727›Full record

ArticleScience translational medicine2021

Toll-like receptor 4-mediated enteric glia loss is critical for the development of necrotizing enterocolitis.

Mark L Kovler, Andres J Gonzalez Salazar, William B Fulton, Peng Lu, Yukihiro Yamaguchi, Qinjie Zhou, Maame Sampah, Asuka Ishiyama, Thomas Prindle, Sanxia Wang and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing 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

64 citing papers in PubMed.

  1. Article
  2. Necrotizing enterocolitis.Nature reviews. Disease primers · 2026
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4 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

14 authors.

Mark L KovlerDivision of Pediatric Surgery, Johns Hopkins University School of Medicine and the Johns Hopkins Children's Center, Baltimore, MD 21287, USA.ORCID 0000-0001-6682-828X
Andres J Gonzalez SalazarDivision of Pediatric Surgery, Johns Hopkins University School of Medicine and the Johns Hopkins Children's Center, Baltimore, MD 21287, USA.ORCID 0000-0002-2672-386X
William B FultonDivision of Pediatric Surgery, Johns Hopkins University School of Medicine and the Johns Hopkins Children's Center, Baltimore, MD 21287, USA.ORCID 0000-0002-5289-1621
Peng LuDivision of Pediatric Surgery, Johns Hopkins University School of Medicine and the Johns Hopkins Children's Center, Baltimore, MD 21287, USA.
Yukihiro YamaguchiDivision of Pediatric Surgery, Johns Hopkins University School of Medicine and the Johns Hopkins Children's Center, Baltimore, MD 21287, USA.
Qinjie ZhouDivision of Pediatric Surgery, Johns Hopkins University School of Medicine and the Johns Hopkins Children's Center, Baltimore, MD 21287, USA.
Maame SampahDivision of Pediatric Surgery, Johns Hopkins University School of Medicine and the Johns Hopkins Children's Center, Baltimore, MD 21287, USA.ORCID 0000-0002-3065-2275
Asuka IshiyamaDivision of Pediatric Surgery, Johns Hopkins University School of Medicine and the Johns Hopkins Children's Center, Baltimore, MD 21287, USA.
Thomas PrindleDivision of Pediatric Surgery, Johns Hopkins University School of Medicine and the Johns Hopkins Children's Center, Baltimore, MD 21287, USA.
Sanxia WangDivision of Pediatric Surgery, Johns Hopkins University School of Medicine and the Johns Hopkins Children's Center, Baltimore, MD 21287, USA.
Hongpeng JiaDivision of Pediatric Surgery, Johns Hopkins University School of Medicine and the Johns Hopkins Children's Center, Baltimore, MD 21287, USA.ORCID 0000-0001-6783-7532
Peter WipfDepartment of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA.ORCID 0000-0001-7693-5863
Chhinder P SodhiDivision of Pediatric Surgery, Johns Hopkins University School of Medicine and the Johns Hopkins Children's Center, Baltimore, MD 21287, USA.
David J HackamDivision of Pediatric Surgery, Johns Hopkins University School of Medicine and the Johns Hopkins Children's Center, Baltimore, MD 21287, USA.ORCID 0000-0001-5195-8807

Funding

Clinical and Laboratory Research Training for Gastrointestinal SurgeonsT32DK007713 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI DAVID J HACKAM · 1996 to 2026
$5.2M
Molecular and metabolic signaling in necrotizing enterocolitisR35GM141956 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI HACKAM, DAVID J · 2021 to 2025
$2.3M
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
Enteric Glia Regulation of Intestinal Epithelial TLR4 Signaling In Necrotizing EnterocolitisR01DK121824 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI HACKAM, DAVID J · 2020 to 2023
$1.4M
NIDDK NIH HHS R01 DK117186NIDDK NIH HHS R01 DK121824NIDDK NIH HHS T32 DK007713NIGMS NIH HHS R35 GM141956
6 · The paper itself

Abstract

Necrotizing enterocolitis (NEC) is a devastating disease of premature infants, whose pathogenesis remains incompletely understood, although activation of the Gram-negative bacterial receptor Toll-like receptor 4 (TLR4) on the intestinal epithelium plays a critical role. Patients with NEC typically display gastrointestinal dysmotility before systemic disease is manifest, suggesting that dysmotility could drive NEC development. Both intestinal motility and inflammation are governed by the enteric nervous system, a network of enteric neurons and glia. We hypothesized here that enteric glia loss in the premature intestine could lead to dysmotility, exaggerated TLR4 signaling, and NEC development. We found that intestinal motility is reduced early in NEC in mice, preceding the onset of intestinal inflammation, whereas pharmacologic restoration of intestinal motility reduced NEC severity. Ileal samples from mouse, piglet, and human NEC revealed enteric glia depletion, and glia-deficient mice (

Indexed as

Enterocolitis, NecrotizingToll-Like Receptor 4AnimalsHumansInfant, NewbornMiceNeurogliaTLR4 protein, humanToll-Like Receptor 4

Identifiers

PMID34550727
PMCPMC8859973

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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.