Dysbiosis of fecal virome in pediatric Crohn's disease and its dynamic changes during infliximab therapy.

UNLABELLED: The gut virome is an emerging but underexplored component of the human microbiota, especially in pediatric Crohn's disease (CD). This study aimed to characterize the fecal virome in children with CD and evaluate its association with clinical response to infliximab (IFX) therapy. A total of 85 participants, including 60 pediatric CD patients and 25 healthy controls (HC), were recruited. Among the CD patients, 53 received ≥3 IFX infusions, 41 achieved remission (IFX-R), and 12 did not (IFX-NR). Viral-like particles in fecal samples were enriched and profiled by metagenomic sequencing, while bacterial communities were assessed via 16S rRNA gene sequencing. Pediatric CD patients exhibited significantly reduced viral richness and altered viral community compared to HCs. Functional analyses revealed that CD patients exhibit a shift in fecal virome function from DNA repair to viral replication and assembly. Trans-kingdom correlations were disrupted in CD, particularly between Torque teno viruses and beneficial bacteria, such as Blautia. An integrated machine learning model combining viral and bacterial markers achieved a certain level of diagnostic accuracy for pediatric CD (area under the curve [AUC] = 89.3%). IFX treatment influences the gut virome, with remission associated with higher abundances of Microviridae and Siphoviridae, while Anelloviridae, Myoviridae, and Podoviridae were enriched in IFX-NR at baseline. These findings suggest the virome as a potential biomarker for predicting clinical outcome in pediatric CD, offering a novel avenue for disease diagnosis and personalized treatment strategies.

IMPORTANCE: Crohn's disease (CD) in children poses a growing clinical challenge, with increasing incidence and variable response to biologic therapies such as infliximab (IFX). While gut bacterial dysbiosis has been extensively studied, the role of the gut virome in pediatric CD remains largely unexplored. This study provides the first longitudinal characterization of the fecal virome in children with CD undergoing IFX therapy. We reveal distinct viral community patterns, functional alterations, and virus-bacteria interactions in pediatric CD patients. Notably, integration of virome and bacteriome profiles enhances diagnostic accuracy, offering a promising avenue for predictive biomarker development. Furthermore, virome changes may be associated with the IFX treatment outcomes in children with CD. These findings highlight the gut virome as a critical but overlooked dimension of host-microbiome interactions in pediatric CD, with potential implications for personalized therapy and mechanistic understanding of treatment resistance.