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

Maria Kulecka, Jill O’Sullivan, Rachel Fitzgerald, Ana Velikonja, Chloe E. Huseyin, Emilio J. Laserna-Mendieta, Patricia Ruiz-Limón, Julia Eckenberger, Miriam Vidal-Marín, Bastian-Alexander Truppel, Raminder Singh, Sandhia Naik, Nicholas M. Croft, Andriy Temko, Aldert Zomer, John MacSharry, Silvia Melgar, Protima Deb, Ian R. Sanderson and Marcus J. Claesson ()
Additional contact information
Maria Kulecka: University College Cork
Jill O’Sullivan: University College Cork
Rachel Fitzgerald: University College Cork
Ana Velikonja: University College Cork
Chloe E. Huseyin: University College Cork
Emilio J. Laserna-Mendieta: University College Cork
Patricia Ruiz-Limón: University College Cork
Julia Eckenberger: University College Cork
Miriam Vidal-Marín: University College Cork
Bastian-Alexander Truppel: University College Cork
Raminder Singh: University College Cork
Sandhia Naik: Barts Health NHS Trust
Nicholas M. Croft: Queen Mary University of London
Andriy Temko: University College Cork
Aldert Zomer: Utrecht University
John MacSharry: University College Cork
Silvia Melgar: University College Cork
Protima Deb: Barts Health NHS Trust
Ian R. Sanderson: Queen Mary University of London
Marcus J. Claesson: University College Cork

Nature Communications, 2025, vol. 16, issue 1, 1-20

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-62533-z

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