A global atlas of the gut virome reveals subtype-specific and functional alterations in irritable bowel syndrome.

The gut virome is a critical component of the microbiome-gut-brain axis; however, its role in irritable bowel syndrome (IBS) remains poorly understood due to limited sample sizes and geographic bias. We aimed to construct a comprehensive global atlas of the IBS gut virome to elucidate its composition, functional potential, and clinical relevance across diverse populations and IBS subtypes. We integrated multi-cohort data comprising 1,104 samples (790 IBS patients and 314 healthy controls) from 11 cohorts across 10 geographic regions. A standardized bioinformatic pipeline was employed to perform viral mining from metagenomic and virus-like particle-enriched metaviromic data. The IBS virome exhibited significant taxonomic alterations, with specific viral signatures distinguishing IBS-D, IBS-C, and IBS-M subtypes. Geographic region was identified as a significant factor influencing the viral community structure. Functionally, the IBS virome was enriched in auxiliary metabolic genes involved in carbon metabolism and neurotransmitter precursor synthesis (histidine and tryptophan metabolism), as well as a distinct profile of virulence factors and antibiotic resistance genes. Furthermore, in a specific cohort, certain viral taxa were significantly correlated with the severity of anxiety and depression. Machine learning models based on viral signatures achieved robust performance for IBS subtyping (area under the curve = 0.92). This study establishes a global baseline for the IBS gut virome, demonstrating that viral communities are dynamically shaped by geography and disease subtypes while encoding gene repertoires with the potential to influence host physiology, thereby providing a foundational resource for precision medicine.IMPORTANCEResearch on the human gut microbiome in IBS has focused primarily on bacteria, leaving the viral component as a vast and poorly understood reservoir. By profiling over 1,000 human samples globally, this study characterizes the taxonomic and functional features of the IBS gut virome. We demonstrate that these viral communities vary across geographic populations and IBS subtypes and are enriched in specific auxiliary metabolic genes, virulence factors, and antibiotic resistance genes. In addition, certain viral profiles show significant correlations with patient psychological symptoms such as anxiety and depression. This study also evaluates the potential of virome-based diagnostic biomarkers. Consequently, our findings provide a valuable reference for future in-depth research into the specific roles and mechanistic contributions of the gut virome in the pathogenesis of IBS.