Evidence map›Paper›PMID 40348872›Full record

ArticlePediatric research2025

Necrotizing enterocolitis: specific human milk oligosaccharides prevent enteric glia loss and hypomotility.

Chhinder P Sodhi, Daniel J Scheese, Cody Tragesser, William B Fulton, Johannes W Duess, Koichi Tsuboi, Maame Efua S Sampah, Rachael H Buck, David R Hill, Anice Sabag-Daigle and 4 more

Abstract read
PubMed Publisher
In one paragraph

Article in Pediatric research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

14 authors.

Chhinder P SodhiDivision of General Pediatric Surgery and Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, MD, USA. csodhi@jhmi.edu.
Daniel J ScheeseDivision of General Pediatric Surgery and Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, MD, USA.
Cody TragesserDivision of General Pediatric Surgery and Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, MD, USA.
William B FultonDivision of General Pediatric Surgery and Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, MD, USA.
Johannes W DuessDivision of General Pediatric Surgery and Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, MD, USA.
Koichi TsuboiDivision of General Pediatric Surgery and Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, MD, USA.
Maame Efua S SampahDivision of General Pediatric Surgery and Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, MD, USA.
Rachael H BuckNutrition Division, Abbott, Columbus, OH, USA.
David R HillNutrition Division, Abbott, Columbus, OH, USA.
Anice Sabag-DaigleNutrition Division, Abbott, Columbus, OH, USA.
Thomas PrindleDivision of General Pediatric Surgery and Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, MD, USA.
Sanxia WangDivision of General Pediatric Surgery and Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, MD, USA.
Menghan WangDivision of General Pediatric Surgery and Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, MD, USA.
David J HackamDivision of General Pediatric Surgery and Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, MD, USA. dhackam1@jhmi.edu.ORCID http://orcid.org/0000-0001-5195-8807

Funding

Molecular and metabolic signaling in necrotizing enterocolitisR35GM141956 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI HACKAM, DAVID J · 2021 to 2025
$2.3M
NIGMS NIH HHS R35 GM141956
6 · The paper itself

Abstract

backgroundNecrotizing enterocolitis (NEC) is mediated by toll-like receptor 4 (TLR4)-induced inflammation and is preceded by reduced intestinal motility. Human milk oligosaccharides (HMOs) are non-digestible components of breast milk that prevent NEC in preclinical models. We now hypothesize that HMOs can reduce the risk of NEC through restoration of intestinal motility and reduced TLR4-mediated inflammation.

methodsNEC was induced in C57-BL/6 mice through the combination of formula gavage, hypoxia, and oral administration of NEC stool. Mice were administered either 2'-FL (5 g/L), 6'-SL (5 g/L), or a blend of 5 specific HMOs (5 g/L) containing 2'-FL (2.606 g/L), 3'-FL (0.652 g/L), LNT (1.304 g/L), 3'-SL (0.174 g/L), and 6'-SL (0.260 g/L). Gastrointestinal motility was assessed by 70 Kd FITC-dextran transit time. Enteric glia were quantified by immunohistochemistry and qRT-PCR expression.

resultsAdministration of either 2'-FL, 6'-SL, or HMO blend significantly attenuated NEC severity and reversed intestinal hypomotility. HMOs prevented enteric glia loss and regulated key genes critical for enteric glia maintenance, attenuated pro-apoptotic genes, and increased anti-apoptotic genes in vitro, resulting in a reduction in apoptosis. Strikingly, HMOs reduced LPS-TLR4-induced NFκB signaling and ROS generation in enteric glia.

conclusionsHMOs protect against NEC at least in part through protective effects on inflammation and the enteric nervous system. IMPACT: This study sheds light on the role of certain human milk oligosaccharides in a clinically relevant mouse model of NEC and adds additional insights into their underlying mechanism of action by revealing a protective effect on the enteric nervous system. These results reveal that HMOs prevent the loss of enteric glia in NEC and influence the expression of genes that regulate enteric glia maintenance. HMOs also limit TLR4-NFkB signaling, providing an additional mechanism of enteric glia maintenance.

Indexed as

Enterocolitis, NecrotizingGastrointestinal MotilityMilk, HumanNeurogliaOligosaccharidesAnimalsDisease Models, AnimalHumansInflammationMiceMice, Inbred C57BLNF-kappa BSignal TransductionToll-Like Receptor 4NF-kappa BOligosaccharidesTlr4 protein, mouseToll-Like Receptor 4

Identifiers

PMID40348872

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.