Evidence map›Paper›PMID 23950179›Full record

ArticleThe Journal of biological chemistry2013

Human milk hyaluronan enhances innate defense of the intestinal epithelium.

David R Hill, Hyunjin K Rho, Sean P Kessler, Ripal Amin, Craig R Homer, Christine McDonald, Mary K Cowman, Carol A de la Motte

Registry-linked trialOpen access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02867605 (Human Pilot Study - HA35), which is not on this map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
5.1field-weighted citation impact, top 4% 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.

NCT02867605 nacompletednot on this mapstarted 2016, after this paper: background citation

Human Pilot Study - HA35 (Hyaluronan Molecular Weight 35) Dietary Supplement for Promoting Intestinal Health

TypeinterventionalSponsorThe Cleveland ClinicRan2016 to 2019Enrolled20ConditionsGastrointestinal MicrobiomeArmsHyaluronan
3 · Its place in the literature

Who cites it

62 citing papers in PubMed, 88 citations in OpenAlex.

  1. Trial
  2. Article
  3. Temporal changes in hyaluronan concentrations in preterm human milk.Journal of perinatology : official journal of the California Perinatal Association · 2026
    Article
  4. Article
  5. Article
  6. Article
  7. 35k Da specific-sized hyaluronan ameliorates high-fat diet-induced liver injury in murine model of moderate obesity.Matrix biology : journal of the International Society for Matrix Biology · 2025
    Article
  8. Article
  9. Article
  10. Review
  11. Evolutionary bridges: how factors present in amniotic fluid and human milk help mature the gut.Journal of perinatology : official journal of the California Perinatal Association · 2024
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. TSG6 hyaluronan matrix remodeling dampens the inflammatory response during colitis.Matrix biology : journal of the International Society for Matrix Biology · 2023
    Article
  18. Review
  19. Over Expression of Cancer Stem Cell Marker CD44 and Its Clinical Significance in Patients with Oral Squamous Cell Carcinoma.Indian journal of otolaryngology and head and neck surgery : official publication of the Association of Otolaryngologists of India · 2023
    Article
  20. Article

2 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

8 authors at 2 institutions in 1 country.

David R HillFrom the Department of Molecular Medicine and.
Hyunjin K Rho
Sean P Kessler
Ripal Amin
Craig R Homer
Christine McDonald
Mary K Cowman
Carol A de la Motte
Cleveland Clinic Lerner College of Medicine · USNew York University · US

Funding

Clinical and Translational Science Collaborative of ClevelandUL1TR000439 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI KONSTAN, MICHAEL W. · 2012 to 2016
$50.0M
Hyaluronan regulation of microbial host defense of the intestineR01HD061918 · NICHD · CLEVELAND CLINIC LERNER COM-CWRU · PI DE LA MOTTE, CAROL A. · 2009 to 2013
$2.0M
Autophagy and Nod2 Function in Crohn's DiseaseR01DK082437 · NIDDK · CLEVELAND CLINIC LERNER COM-CWRU · PI MCDONALD, CHRISTINE L · 2009 to 2013
$1.6M
NCATS NIH HHS UL1 TR000439NICHD NIH HHS HD061918NICHD NIH HHS R01 HD061918NIDDK NIH HHS R01 DK082437NIDDK NIH HHS R01DK82437
6 · The paper itself

Abstract

Breast-feeding is associated with enhanced protection from gastrointestinal disease in infants, mediated in part by an array of bioactive glycan components in milk that act through molecular mechanisms to inhibit enteric pathogen infection. Human milk contains hyaluronan (HA), a glycosaminoglycan polymer found in virtually all mammalian tissues. We have shown that synthetic HA of a specific size range promotes expression of antimicrobial peptides in intestinal epithelium. We hypothesize that hyaluronan from human milk also enhances innate antimicrobial defense. Here we define the concentration of HA in human milk during the first 6 months postpartum. Importantly, HA isolated from milk has a biological function. Treatment of HT-29 colonic epithelial cells with human milk HA at physiologic concentrations results in time- and dose-dependent induction of the antimicrobial peptide human β-defensin 2 and is abrogated by digestion of milk HA with a specific hyaluronidase. Milk HA induction of human β-defensin 2 expression is also reduced in the presence of a CD44-blocking antibody and is associated with a specific increase in ERK1/2 phosphorylation, suggesting a role for the HA receptor CD44. Furthermore, oral administration of human milk-derived HA to adult, wild-type mice results in induction of the murine Hβ D2 ortholog in intestinal mucosa and is dependent upon both TLR4 and CD44 in vivo. Finally, treatment of cultured colonic epithelial cells with human milk HA enhances resistance to infection by the enteric pathogen Salmonella typhimurium. Together, our observations suggest that maternally provided HA stimulates protective antimicrobial defense in the newborn.

Indexed as

Administration, OralAnimalsAntibodiesbeta-DefensinsCell MembraneColony Count, MicrobialDisease ResistanceExtracellular Signal-Regulated MAP KinasesFemaleHT29 CellsHumansHyaluronan ReceptorsHyaluronic AcidImmunity, InnateIntestinal MucosaLactationAntibodiesbeta-DefensinsExtracellular Signal-Regulated MAP KinasesHyaluronan ReceptorsHyaluronic AcidToll-Like Receptor 4Cd44DefensinsEpitheliumHost DefenseHuman MilkHyaluronateSalmonella InfectionToll-like Receptors (TLR)

Identifiers

PMID23950179
PMCPMC3790008
OpenAlexW2036294650

What OpenQuestion holds

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Read underepoch 390

Registered trials

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.