Beyond bacterial dysbiosis: the emerging role of gut bacteriophages in type 2 diabetes

Abstract

Bacteriophages, the viruses that infect gut bacteria, are now seen as active members of the intestinal ecosystem rather than passive observers. In type 2 diabetes mellitus (T2DM), growing evidence suggests that the gut phage community changes in several important ways. People with T2DM often have lower phage diversity, more temperate phages, and shifts in bacterial hosts. These changes may spread through the microbial network, affecting gene exchange, bacterial metabolism, and immune activity. Through these pathways, phages may contribute to microbial and immune alterations associated with insulin resistance and the chronic inflammation that characterizes T2DM, even though direct proof of causality is still missing. Diet and metabolic stress also influence how phages behave, including their replication cycles and host preferences. This means that environmental factors can constantly reshape the gut virome and, in turn, affect metabolic health. Recognizing this link moves the focus beyond bacterial imbalance to a broader concept of phage-mediated metabolic dysregulation, in which viruses may represent underrecognized contributors to energy balance and inflammation. Understanding these interactions may reveal new microbial targets and guide the development of phage-based or microbiome-based approaches for the prevention and treatment of T2DM.