Metagenomic analysis of the human gut virome reveals functional signatures and viral stability across hospitalized and non-hospitalized 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, we identified 309 putative vAMGs spanning 90 functional categories, primarily related to metabolism and environmental information processing. Non-diarrheic individuals harbored a higher number and diversity of vAMGs compared to hospitalized groups (Kruskal–Wallis, p < 0.01), whereas ICU and Non-ICU patients showed reduced and more variable functional profiles. Beta diversity analysis revealed that diarrhea status, rather than hospitalization per se, was associated with modest but significant shifts in functional composition (PERMANOVA, R² = 0.047, p = 0.025), driven by quantitative changes in shared AMGs rather than the presence of unique functions. Notably, resistance-related vAMGs, including bacitracin transporters and Zinc D-Ala-D-Ala carboxypeptidase, were detected across samples, highlighting the potential of phages as mobile reservoirs of antibiotic resistance. Conclusion: Together, our findings indicate that hospitalization and diarrhea do not markedly alter the taxonomic structure of the gut virome but are associated with modest shifts in viral functional potential. The maintenance of a stable viral community alongside variable AMG repertoires suggests that phages may modulate host–microbiome interactions primarily through functional fine-tuning rather than large-scale community restructuring. Our study provides evidence for the ecological resilience of the human gut virome and underscores the need to integrate viral communities into resistome research.