Context-dependent roles of ketone metabolism in intestinal inflammation

Ketone metabolism is traditionally viewed as an alternative metabolic pathway providing energy during carbohydrate deprivation through the production and utilization of ketone bodies. Ketone bodies also function as signaling molecules regulating immune and metabolic processes. Accumulating evidence shows that ketone metabolism influences diverse diseases and immune responses, including inflammation, autoimmunity, and infection. Recently, ketone metabolism has been associated with inflammatory bowel disease (IBD), a chronic inflammatory disorder of the intestine, although reported effects are heterogeneous and context-dependent. In this review, we synthesize current evidence on ketone metabolism in IBD and intestinal inflammation, highlighting its roles in barrier integrity, immune regulation, and microbiota interactions. We also discuss potential mechanisms underlying divergent outcomes and outline key questions for future research.