Gut Virome–Host Interactions in Metabolic Health: From Immune Regulation to Glucose Homeostasis and Diabetes

The gut microbiome plays an important role in metabolic regulation, but the role of its viral component remains poorly understood. This review examines how bacteriophages and eukaryotic viruses may influence immune regulation, glucose homeostasis, and diabetes. A structured narrative search of PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar was conducted. English-language studies published between 1996 and October 2026 were considered, with emphasis on literature published from 2010 onward. Human studies have reported altered phage abundance and disease-associated phage operational taxonomic units in type 2 diabetes. Reduced virome diversity has also been observed before islet-autoantibody seroconversion in children at risk of type 1 diabetes. Mechanistically, viral nucleic acids and phage-derived components may activate Toll-like receptor, NF-κB, MAPK, and interferon signaling. Phages may also reshape bacterial communities through lysis, lysogeny, and horizontal gene transfer. These changes could influence intestinal barrier integrity, microbial translocation, and the production of short-chain fatty acids, secondary bile acids, and tryptophan-derived metabolites. These pathways may, in turn, affect inflammation and insulin signaling. However, available studies vary considerably in design, sampling methods, virome-analysis techniques, and metabolic outcomes. Most evidence remains associative, indirect, or preclinical. Direct causal relationships between specific virome patterns, diabetes, and postprandial glucose responses have not been established. Longitudinal multi-omics studies incorporating continuous glucose monitoring and controlled experimental models are needed to clarify causality and determine the predictive and therapeutic value of the gut virome.