Commensal gut virome regulates intestinal nutrient sensing via Th17 cells

The enteric microbiome and nutrient sensing in the small intestine play critical roles in maintaining host metabolic homeostasis. However, insight is limited to bacteria and fungi. The role of the enteric virome remains poorly understood. Here, we demonstrate that the enteric virome significantly influences carbohydrate digestion and absorption independently of bacteriome. Furthermore, the virome elicits distinct responses across different intestinal cell types. Specifically, it activates programs for carbohydrate digestion and absorption in intestinal epithelial cells, while simultaneously stimulating antigen presenting cells-Th17 cells to produce interleukin-22, a cytokine that curbs excessive carbohydrate uptake. The viromes effect on carbohydrate digestion and absorption--suppressive or stimulatory--depends on the presence or absence of immune surveillance. This intricate metabolic-immune interplay underscores the enteric virome as a pivotal regulator of host metabolism, and highlights its potential as a therapeutic target for metabolic disorders.