Acetate mediates a microbiome-brain-β-cell axis to promote metabolic syndrome.

Abstract

Obesity, insulin resistance and the metabolic syndrome are associated with changes to the gut microbiota; however, the mechanism by which modifications to the gut microbiota might lead to these conditions is unknown. Here we show that increased production of acetate by an altered gut microbiota leads to activation of the parasympathetic nervous system which in turn promotes increased glucose-stimulated insulin secretion (GSIS), increased ghrelin secretion, hyperphagia, obesity and its related sequelae (Extended Data Fig. 1). Taken together, these data identify increased acetate production by a nutrient-gut microbiota interaction and subsequent parasympathetic activation as possible therapeutic targets for obesity.