Overview of ketone body metabolism in small and large intestine. HMGCS2 distribution and the roles of βOHB in the small and large intestine vary. In small intestine, βOHB triggers Notch signaling and Th17 immunomodulatory changes. In large intestine, anaerobic bacterial fermentation yields butyrate, a source of βOHB that influences the gut community. Abbreviations: βOHB, β-hydroxybutyrate; HDAC, histone deacetylase; HMGCS2, 3-hydroxymethylglutaryl-CoA synthase. Figure adapted from images created with BioRender.com.