The human gut virome at the crossroads of immunity, disease and therapeutics: a comprehensive review

Abstract

The human gut virome, a complex and dynamic part of the gut microbiome, is an important but understudied mediator of health and disease. Encompassing bacteriophages, eukaryotic viruses, and endogenous viral elements, the gut virome is intricately linked to bacteriome, immune, and host metabolic systems, which impacts the development of diseases including inflammatory bowel disease (IBD) and metabolic diseases, and even neuropsychiatric and autoimmune diseases. The development of metagenomic sequencing techniques over the past few years has brought to light the high degree of interindividual variability of the virome, as well as its rapid response to environmental factors such as diet and antibiotics, and its age-dependent evolution. Dysbiosis in viral communities—characterized by changes in activity of temperate phages, reductions in viral diversity, or expansion of pathogenic viruses—are associated with mucosal inflammation, microbial dysbiosis, and systemic disease. Novel treatments under development, including fecal virome transplantation (FVT) and targeted phage therapy, demonstrate the potential of the virome in re-establishing microbial balance and combatting antibiotic resistant infections. Yet, obstacles exist in organizing virome characterization, determining causal associations, and guaranteeing safety of viral-based treatment modalities. The focus of this review is to integrate current insights into the diversity and stability, as well as functional attributes of the gut virome, while stressing its reciprocal relationships with host immunity and disease development. It investigates the virome in other settings, such as inflammatory bowel disease (IBD), type 1 and type 2 diabetes, obesity, liver diseases, arthritis and neuropsychiatric conditions, and how diet, stress and geography influence viral ecology. By combining multi-omics strategies with the personalized aspect of the virome, new biomarkers and precision therapies could be discovered in the future. This study highlights the virome as an important frontier in microbiome research with potentially transformative implications for diagnostics, therapeutics, and preventive medicine in the context of personalized health.