Targeting the gut virome: Plant-derived compounds alter bacteriophage dynamics in a murine inflammatory bowel disease model

Gut bacteriophages (phages) are key regulators of microbial ecology and host immune interactions; yet their roles in the pathogenesis of inflammatory bowel disease (IBD) and responses to therapy remain incompletely understood. In this study, metagenomic sequencing was employed to characterise phage community alterations in a trinitrobenzene sulfonic acid (TNBS)-induced murine colitis model and to evaluate the potential modulatory effects of dexamethasone (DEX) and two novel galloyl glucosides−galloyl-lawsoniaside A (comp-4) and uromyrtoside (comp-6) isolated from Uromyrtus metrosideros. TNBS administration was associated with reduced phage alpha diversity, disruption of community structure, and depletion of key taxa such as Caudoviricetes sp. isolate ct04m9, which are commonly linked with beneficial bacterial populations. Therapeutic intervention with DEX and plant-derived compounds appeared to partially restore phage diversity and revealed the presence of previously underrepresented taxa, including Faecalibacterium phage FP_Lagaffe, associated with the anti-inflammatory commensal F. prausnitzii. Network and differential abundance analyses identified distinct treatment-associated phage signatures, while correlation profiling uncovered structured, non-random phage–host associations, indicating ecological specificity and functional relevance. Positive correlations with colitis-associated taxa such as Clostridium innocuum and Bacteroides spp. may reflect cooperative microbial dynamics, whereas negative associations with members of the Muribaculaceae family imply potential phage-mediated control of dysbiotic populations. These findings highlight the dynamic and disease-responsive nature of the gut-virome and suggest that modulation of phages communities by plant-derived compounds may represent a promising avenue for restoring intestinal microbial in IBD.