Gut virome instability in HSCT

Abstract

The gut virome remains one of the least resolved components of the human microbiome, limiting interpretation of how viral communities shape intestinal injury and recovery. Hematopoietic stem cell transplantation (HSCT), particularly in the allogeneic setting, offers an informative human model of gut virome instability because conditioning-related epithelial injury, profound immune depletion, delayed immune reconstitution, antimicrobial and antiviral pressure, and graft-versus-host disease (GvHD) converge over a short time window to destabilize the intestinal ecosystem. In this context, the gut virome is best understood not only as a reservoir of reactivating pathogens, but as a clinically informative ecological layer linking mucosal vulnerability, bacterial network instability, metabolite loss, infection risk, and post-transplant recovery. Emerging human studies show that post-transplant virome signals are dynamic, individualized, and compartment-dependent. Longitudinal stool profiling has revealed viral blooms, enrichment of persistent DNA viruses, reduced phage richness, and cross-kingdom ecological disruption in association with enteric GvHD. Targeted enteric viral studies and biopsy-based analyses further indicate that stool, blood, and tissue viral signals are not clinically interchangeable, and that broader virologic interrogation may uncover intestinal viral activity not captured by routine plasma surveillance alone. Multi-omics evidence now extends this view by linking bacteriophage-associated bacterial consortia to protective intestinal metabolites and outcome-related ecological states. These advances shift the field from single-virus interpretation toward a cross-kingdom model of injury and recovery. The next step is to convert association-rich viromics into longitudinal, compartment-aware, and intervention-linked frameworks that can support ecological risk stratification and more precise supportive care in HSCT.