Combining mucosal microbiome and host multi-omics data shows prognostic potential in paediatric ulcerative colitis
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<sup>-/-</sup> 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
- Nicholas M. Croft (ORCID: https://orcid.org/0000-0002-1519-6435)
- Andriy Temko (ORCID: https://orcid.org/0000-0001-6548-0971)
- Rachel S. Fitzgerald (ORCID: https://orcid.org/0000-0002-5569-6311)
- Sandhia Naik (ORCID: https://orcid.org/0000-0002-9038-0646)
- Maria Kulecka (ORCID: https://orcid.org/0000-0002-9830-8892)
- Julia Eckenberger (ORCID: https://orcid.org/0000-0003-4781-0660)
- Aldert Zomer (ORCID: https://orcid.org/0000-0002-0758-5190)
- Chloe E. Huseyin (ORCID: https://orcid.org/0000-0002-7517-3980)
- John MacSharry (ORCID: https://orcid.org/0000-0002-9528-6261)
- Marcus Joakim Claesson (ORCID: https://orcid.org/0000-0002-5712-0623)
- Ian R. Sanderson (ORCID: https://orcid.org/0000-0002-9814-0161)
- Silvia Melgar (ORCID: https://orcid.org/0000-0001-7463-3343)
- Patricia Ruiz‐Limón (ORCID: https://orcid.org/0000-0003-3820-428X)
- Raminder Singh (ORCID: https://orcid.org/0000-0002-5348-4112)
- Protima Deb
- Emilio J. Laserna‐Mendieta (ORCID: https://orcid.org/0000-0002-9039-7667)
- Janet OʼSullivan
- Bastian-Alexander Truppel
- Ana Velikonja
- Miriam Vidal-Marín
Institutions
- Queen Mary University of London (GB)
- Utrecht University (NL)
- Barts Health NHS Trust (GB)
- University College Cork (IE)
- APC Microbiome Institute (IE)
- Hospital Clínico Universitario Virgen de la Victoria (ES)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-08-04
- DOI
- https://doi.org/10.1038/s41467-025-62533-z
- Citations
- 1
- Primary Topic
- Gut microbiota and health
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- Crohn's and Colitis Foundation
- European Commission
- Science Foundation Ireland
- University College Cork
- Barts Health NHS Trust
- Instituto de Salud Carlos III