Metagenomic Analysis of the Human Gut Virome Reveals Functional Signatures and Viral Stability in Diarrheal and Non-Diarrheal Individuals

Background The human gut virome is a fundamental yet understudied component of the intestinal microbiome. However, its taxonomic composition and functional potential in Latin American populations remain poorly understood, particularly under clinical stressors such as hospitalization and diarrhea conditions often linked to microbial dysbiosis Methods We conducted a hybrid metagenomic analysis of the human gut virome from 37 fecal samples: 10 from patients admitted to intensive care units (ICU), 13 from hospitalized patients outside the ICU (Non-ICU), and 14 from non-diarrheic individuals, including taxonomic and functional profiling of viruses and detection of viral auxiliary metabolic genes (vAMGs). Results We identified 494 high-quality viral vOTUs, from which 37,619 ORFs were predicted. Taxonomically, Caudoviricetes and Intestiviridae were consistently present across all groups, supporting their role as part of a conserved core virome. Functionally, non-diarrheic individuals harbored more viral metabolic auxiliary genes (vAMGs) related to genetic recombination, suggesting a greater prevalence of temperate phages. We also identified resistance-related vAMGs, including ATP-dependent bacitracin transporters and Zinc D-Ala-D-Ala carboxypeptidase, highlighting the potential of phages as mobile reservoirs of antibiotic resistance. Conclusion Altogether, our findings reveal the coexistence of lytic and lysogenic strategies in the gut virome, shaped by clinical context. Our study provides evidence for the ecological resilience of the human gut virome and underscores the need to integrate viral communities into resistome research.