Dietary sugar intake is associated with various metabolic disorders. A study by Anderson et al describes an arctic population whose genetic variation in sucrase-isomaltase (SI), an intestinal sucrose breakdown enzyme, confers a healthier anthropometric and metabolic profile in human adults. Interestingly, such beneficial effects are not associated with reduced sucrose intake but are related to increased acetate production from sucrose catabolism by gut microbiota. While further investigations will be required to elucidate molecular mechanisms, this study raises an exciting possibility of targeting SI for therapeutic intervention of metabolic diseases.