Soluble dietary fibers induce metabolic benefits on body weight and glycemic control, but the underlying mechanisms are still poorly understood. Intestinal gluconeogenesis (IGN) exerts beneficial effects on energy and glucose homeostasis. We have shown that short-chain fatty acids (SCFA), such as propionate and butyrate, which are produced from the fermentation of soluble fibers by the intestinal microbiota, activate IGN by complementary mechanisms. Butyrate activates gene expression of IGN via a cAMP-dependent mechanism, whereas propionate, itself a precursor of IGN, activates intestine gene expression through a reflex arc involving the free fatty acid receptor FFAR3. Metabolic benefits on body weight and glucose control induced by SCFA or dietary fibers in normal mice are absent in mice deficient for IGN, despite similar changes in the composition of the intestinal microbiota. Thus, IGN is a causal link in the metabolic benefits associated to soluble fibers.