Bacteriophages from T2D drive human inflammatory response. null

Individuals with type 2 diabetes (T2D) show signs of low-grade inflammation, which is related to the development of insulin resistance and beta-cell dysfunction. However, the underlying triggers remain unknown. The gut microbiota is a plausible source as it comprises pro-inflammatory bacteria, bacterial metabolites and viruses, including (bacterio)phages. These prokaryotic viruses have been shown to mediate inflammatory responses in gastrointestinal disease. Given the differences in phage populations in healthy individuals versus those with cardiometabolic diseases such as T2D, we here questioned if phages from T2D individuals would have increased immunogenic potential. To address this, we isolated intestinal phage from a fresh stool sample of healthy controls and individuals with newly diagnosed, treatment naive T2D. Phages were purified using cesium chloride ultracentrifugation and incubated with healthy donor dendritic cells (DCs) as well as T cells. Donors with T2D had slightly higher free viral particle numbers compared to healthy controls (p = 0.1972), which has been previously associated with disease states. Further, phages from T2D induced a higher inflammatory response in DCs and T cells. For example, the antigen presentation marker CD86 on DCs (p < 0.001) and interferon-y secretion from T cells (p < 0.01) was increased when comparing the two groups. These results suggest that phages might play a role in low-grade inflammation in T2D individuals.