Combining mucosal microbiome and host multi-omics data shows prognostic potential in paediatric ulcerative colitis
Loading...
Files
Accepted Version
Date
2025
Authors
Kulecka, Maria
O'Sullivan, Jill
Fitzgerald, Rachel
Velikonja, Ana
Huseyin, Chloe E.
Laserna-Mendieta, Emilio J.
Ruiz-Limón, Patricia
Eckenberger, Julia
Vidal-Marin, Miriam
Truppel, Bastian-Alexander
Journal Title
Journal ISSN
Volume Title
Publisher
Nature Publishing Group
Published Version
Abstract
Current first-line treatments of paediatric ulcerative colitis (UC) maintain 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 and genotyping, and in vitro and in vivo experiments on selected bacteria. Baseline bacterial diversity was lower in relapsing children, who had fewer butyrate-producers but more oral-associated bacteria, whereof Veilonella parvula induced inflammation in epithelial cell lines and IL10-/- mice. Microbiota had the strongest association with future relapse, followed by epigenome and transcriptome. Relapse-prediction from separate omics data was outperformed by a robust machine learning approach combining microbiomes and epigenomes. In summary, combinatory machine learning of host-microbe data, especially microbiome and epigenome, had prognostic potential in paediatric UC. Our translational findings also suggest that pro-inflammatory oral-associated colonizers can exploit reduced colonic bacterial diversity of relapsing children.
Description
Keywords
Paediatric ulcerative colitis , Microbiome , Machine learning , Multi-omics , Treatment failure , Treatment outcome
Citation
Kulecka, M., O'Sullivan, J., Fitzgerald, R., Velikonja, A., Huseyin, C. E., Laserna-Mendieta, E. J., Ruiz-Limón, P., Eckenberger, J., Vidal-Marin, M., Truppel, B-A., Singh, R., Naik, S., Croft, N. M., Temko, A., Zomer, A., Melgar, S., Deb, P., Sanderson, I. R. and Claesson, M. J. (2025) 'Combining mucosal microbiome and host multi-omics data shows prognostic potential in paediatric ulcerative colitis', Nature Communications, (40 pp).