Combining mucosal microbiome and host multi-omics data shows prognostic potential in paediatric ulcerative colitis.

Journal: Nature communications
Published Date:

Abstract

Current first-line treatments of paediatric ulcerative colitis (UC) maintain a 6-month remission in only half of the patients. Relapse prediction at diagnosis could enable earlier introduction of immunosuppressants. We collected intestinal biopsies from 56 treatment-naïve children, combining mucosal quantitative microbial profiling with host epigenomics, transcriptomics, genotyping, and in vitro and in vivo experiments on selected bacteria. Baseline bacterial diversity is lower in relapsing children, who have fewer butyrate producers but more oral-associated bacteria, whereof Veillonella parvula induces inflammation in epithelial cell lines and IL10 mice. Microbiota has the strongest association with future relapse, followed by host epigenome and transcriptome. Interferon gamma signalling is also linked to relapse-associated bacteria. Relapse-prediction using separate omics data is outperformed by a robust machine learning approach combining microbiomes and epigenomes. In summary, host-microbe data have prognostic potential in paediatric UC. Our translational findings also suggest that pro-inflammatory oral-associated colonizers can exploit the reduced colonic bacterial diversity of relapsing children.

Authors

  • Maria Kulecka
    APC Microbiome Ireland, University College Cork, Cork, Ireland.
  • Jill O'Sullivan
    APC Microbiome Ireland, University College Cork, Cork, Ireland.
  • Rachel Fitzgerald
    APC Microbiome Ireland, University College Cork, Cork, Ireland.
  • Ana Velikonja
    APC Microbiome Ireland, University College Cork, Cork, Ireland.
  • Chloe E Huseyin
    APC Microbiome Ireland, University College Cork, Cork, Ireland.
  • Emilio J Laserna-Mendieta
    APC Microbiome Ireland, University College Cork, Cork, Ireland.
  • Patricia Ruiz-Limón
    APC Microbiome Ireland, University College Cork, Cork, Ireland.
  • Julia Eckenberger
    APC Microbiome Ireland, University College Cork, Cork, Ireland.
  • Miriam Vidal-Marín
    APC Microbiome Ireland, University College Cork, Cork, Ireland.
  • Bastian-Alexander Truppel
    APC Microbiome Ireland, University College Cork, Cork, Ireland.
  • Raminder Singh
    APC Microbiome Ireland, University College Cork, Cork, Ireland.
  • Sandhia Naik
    Paediatric Gastroenterology, Barts Health NHS Trust, London, UK.
  • Nicholas M Croft
    Centre for Immunobiology, Blizard Institute, Queen Mary University of London, London, UK.
  • Andriy Temko
    Neonatal Brain Research Group, Irish Centre for Fetal and Neonatal Translational Research (INFANT), Ireland; Department of Electrical and Electronics Engineering, University College Cork, Ireland.
  • Aldert Zomer
    Department of Pediatrics, Laboratory of Pediatric Infectious Diseases, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
  • John MacSharry
    APC Microbiome Ireland, University College Cork, Cork, Ireland.
  • Silvia Melgar
    APC Microbiome Ireland, University College Cork, Cork, Ireland.
  • Protima Deb
    Paediatric Gastroenterology, Barts Health NHS Trust, London, UK.
  • Ian R Sanderson
    Centre for Immunobiology, Blizard Institute, Queen Mary University of London, London, UK.
  • Marcus J Claesson
    School of Microbiology and APC Microbiome Ireland, University College Cork, Cork, Ireland.