The mechanism of keto-diet-induced β-hydroxybutyrate regulating intestinal microbiota and short-chain fatty acid metabolism

This study examined how a ketogenic diet and its main metabolite, β-hydroxybutyrate, change gut bacteria and short-chain fatty acid (SCFA) production in diabetic mice. C57BL/6J mice were fed a ketogenic diet for eight weeks. Gut bacteria were analyzed by 16S rRNA sequencing, and fecal SCFAs were measured using gas chromatography. The integrity of the intestinal barrier was tested by ZO-1 staining. The ketogenic diet raised Lactobacillus and Bacteroides levels by about 3.4 times, and butyrate and acetate concentrations increased by 41% and 29%, respectively. Serum β-hydroxybutyrate showed a positive link with butyrate (ρ = 0.48, P < 0.01). Mice in the ketogenic group also showed higher ZO-1 expression and lower gut permeability. These results suggest that ketogenic feeding may improve gut barrier function and insulin response through the β-hydroxybutyrate–butyrate pathway. This finding provides a possible dietary strategy for better metabolic control in type 2 diabetes.