IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-21356-4.html
   My bibliography  Save this article

Maternal aryl hydrocarbon receptor activation protects newborns against necrotizing enterocolitis

Author

Listed:
  • Peng Lu

    (Johns Hopkins University School of Medicine and the Johns Hopkins Children’s Center)

  • Yukihiro Yamaguchi

    (Johns Hopkins University School of Medicine and the Johns Hopkins Children’s Center)

  • William B. Fulton

    (Johns Hopkins University School of Medicine and the Johns Hopkins Children’s Center)

  • Sanxia Wang

    (Johns Hopkins University School of Medicine and the Johns Hopkins Children’s Center)

  • Qinjie Zhou

    (Johns Hopkins University School of Medicine and the Johns Hopkins Children’s Center)

  • Hongpeng Jia

    (Johns Hopkins University School of Medicine and the Johns Hopkins Children’s Center)

  • Mark L. Kovler

    (Johns Hopkins University School of Medicine and the Johns Hopkins Children’s Center)

  • Andres Gonzalez Salazar

    (Johns Hopkins University School of Medicine and the Johns Hopkins Children’s Center)

  • Maame Sampah

    (Johns Hopkins University School of Medicine and the Johns Hopkins Children’s Center)

  • Thomas Prindle

    (Johns Hopkins University School of Medicine and the Johns Hopkins Children’s Center)

  • Peter Wipf

    (University of Pittsburgh)

  • Chhinder P. Sodhi

    (Johns Hopkins University School of Medicine and the Johns Hopkins Children’s Center)

  • David J. Hackam

    (Johns Hopkins University School of Medicine and the Johns Hopkins Children’s Center)

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.

Suggested Citation

  • Peng Lu & Yukihiro Yamaguchi & William B. Fulton & Sanxia Wang & Qinjie Zhou & Hongpeng Jia & Mark L. Kovler & Andres Gonzalez Salazar & Maame Sampah & Thomas Prindle & Peter Wipf & Chhinder P. Sodhi , 2021. "Maternal aryl hydrocarbon receptor activation protects newborns against necrotizing enterocolitis," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21356-4
    DOI: 10.1038/s41467-021-21356-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-21356-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-21356-4?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Kelsey E. Johnson & Nelmary Hernandez-Alvarado & Mark Blackstad & Timothy Heisel & Mattea Allert & David A. Fields & Elvira Isganaitis & Katherine M. Jacobs & Dan Knights & Eric F. Lock & Michael C. R, 2024. "Human cytomegalovirus in breast milk is associated with milk composition and the infant gut microbiome and growth," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21356-4. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.