IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-018-07841-3.html
   My bibliography  Save this article

Ulcerative colitis mucosal transcriptomes reveal mitochondriopathy and personalized mechanisms underlying disease severity and treatment response

Author

Listed:
  • Yael Haberman

    (Cincinnati Children’s Hospital Medical Center, and the University of Cincinnati College of Medicine
    Tel Hashomer, affiliated with the Tel Aviv University)

  • Rebekah Karns

    (Cincinnati Children’s Hospital Medical Center, and the University of Cincinnati College of Medicine)

  • Phillip J. Dexheimer

    (Cincinnati Children’s Hospital Medical Center, and the University of Cincinnati College of Medicine)

  • Melanie Schirmer

    (Broad Institute of MIT and Harvard University)

  • Judith Somekh

    (Technion
    University of Haifa)

  • Ingrid Jurickova

    (Cincinnati Children’s Hospital Medical Center, and the University of Cincinnati College of Medicine)

  • Tzipi Braun

    (Tel Hashomer, affiliated with the Tel Aviv University)

  • Elizabeth Novak

    (Children’s Hospital of Pittsburgh)

  • Laura Bauman

    (Cincinnati Children’s Hospital Medical Center, and the University of Cincinnati College of Medicine
    University of California at San Diego)

  • Margaret H. Collins

    (Cincinnati Children’s Hospital Medical Center, and the University of Cincinnati College of Medicine)

  • Angela Mo

    (Georgia Institute of Technology)

  • Michael J. Rosen

    (Cincinnati Children’s Hospital Medical Center, and the University of Cincinnati College of Medicine)

  • Erin Bonkowski

    (Cincinnati Children’s Hospital Medical Center, and the University of Cincinnati College of Medicine)

  • Nathan Gotman

    (University of North Carolina)

  • Alison Marquis

    (University of North Carolina)

  • Mason Nistel

    (Cincinnati Children’s Hospital Medical Center, and the University of Cincinnati College of Medicine)

  • Paul A. Rufo

    (Harvard—Children’s Hospital Boston)

  • Susan S. Baker

    (Women & Children’s Hospital of Buffalo WCHOB)

  • Cary G. Sauer

    (Emory University)

  • James Markowitz

    (Cohen Children’s Medical Center of New York)

  • Marian D. Pfefferkorn

    (Riley Hospital for Children)

  • Joel R. Rosh

    (Goryeb Children’s Hospital—Atlantic Health)

  • Brendan M. Boyle

    (Nationwide Children’s Hospital)

  • David R. Mack

    (Children’s Hospital of East Ontario, Ottawa)

  • Robert N. Baldassano

    (The Children’s Hospital of Philadelphia)

  • Sapana Shah

    (Children’s Hospital of Pittsburgh of UPMC)

  • Neal S. Leleiko

    (Hasbro Children’s Hospital)

  • Melvin B. Heyman

    (University of California at San Francisco)

  • Anne M. Grifiths

    (Hospital for Sick Children)

  • Ashish S. Patel

    (UT Southwestern)

  • Joshua D. Noe

    (Medical College of Wisconsin)

  • Bruce J. Aronow

    (Cincinnati Children’s Hospital Medical Center, and the University of Cincinnati College of Medicine)

  • Subra Kugathasan

    (Emory University)

  • Thomas D. Walters

    (Hospital for Sick Children)

  • Greg Gibson

    (Georgia Institute of Technology)

  • Sonia Davis Thomas

    (University of North Carolina
    RTI International)

  • Kevin Mollen

    (Children’s Hospital of Pittsburgh)

  • Shai Shen-Orr

    (Technion)

  • Curtis Huttenhower

    (Broad Institute of MIT and Harvard University
    Harvard School of Public Health)

  • Ramnik J. Xavier

    (Broad Institute of MIT and Harvard University
    Harvard Medical School)

  • Jeffrey S. Hyams

    (Connecticut Children’s Medical Center)

  • Lee A. Denson

    (Cincinnati Children’s Hospital Medical Center, and the University of Cincinnati College of Medicine)

Abstract

Molecular mechanisms driving disease course and response to therapy in ulcerative colitis (UC) are not well understood. Here, we use RNAseq to define pre-treatment rectal gene expression, and fecal microbiota profiles, in 206 pediatric UC patients receiving standardised therapy. We validate our key findings in adult and paediatric UC cohorts of 408 participants. We observe a marked suppression of mitochondrial genes and function across cohorts in active UC, and that increasing disease severity is notable for enrichment of adenoma/adenocarcinoma and innate immune genes. A subset of severity genes improves prediction of corticosteroid-induced remission in the discovery cohort; this gene signature is also associated with response to anti-TNFα and anti-α4β7 integrin in adults. The severity and therapeutic response gene signatures were in turn associated with shifts in microbes previously implicated in mucosal homeostasis. Our data provide insights into UC pathogenesis, and may prioritise future therapies for nonresponders to current approaches.

Suggested Citation

  • Yael Haberman & Rebekah Karns & Phillip J. Dexheimer & Melanie Schirmer & Judith Somekh & Ingrid Jurickova & Tzipi Braun & Elizabeth Novak & Laura Bauman & Margaret H. Collins & Angela Mo & Michael J., 2019. "Ulcerative colitis mucosal transcriptomes reveal mitochondriopathy and personalized mechanisms underlying disease severity and treatment response," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-018-07841-3
    DOI: 10.1038/s41467-018-07841-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-07841-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-018-07841-3?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. Tzipi Braun & Rui Feng & Amnon Amir & Nina Levhar & Hila Shacham & Ren Mao & Rotem Hadar & Itamar Toren & Yadid Algavi & Kathleen Abu-Saad & Shuoyu Zhuo & Gilat Efroni & Alona Malik & Orit Picard & Mi, 2024. "Diet-omics in the Study of Urban and Rural Crohn disease Evolution (SOURCE) cohort," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Jorge Mata-Garrido & Yao Xiang & Yunhua Chang-Marchand & Caroline Reisacher & Elisabeth Ageron & Ida Chiara Guerrera & Iñigo Casafont & Aurelia Bruneau & Claire Cherbuy & Xavier Treton & Anne Dumay & , 2022. "The Heterochromatin protein 1 is a regulator in RNA splicing precision deficient in ulcerative colitis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Johanne Brooks-Warburton & Dezso Modos & Padhmanand Sudhakar & Matthew Madgwick & John P. Thomas & Balazs Bohar & David Fazekas & Azedine Zoufir & Orsolya Kapuy & Mate Szalay-Beko & Bram Verstockt & L, 2022. "A systems genomics approach to uncover patient-specific pathogenic pathways and proteins in ulcerative colitis," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    4. Joachim Hanna & Flavio Beke & Louise M. O’Brien & Chrysa Kapeni & Hung-Chang Chen & Valentina Carbonaro & Alexander B. Kim & Kamal Kishore & Timon E. Adolph & Mikkel-Ole Skjoedt & Karsten Skjoedt & Ma, 2022. "Cell-autonomous Hedgehog signaling controls Th17 polarization and pathogenicity," Nature Communications, Nature, vol. 13(1), pages 1-18, 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:10:y:2019:i:1:d:10.1038_s41467-018-07841-3. 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.