Leveraging the Gut to Treat Metabolic Disease

25 years ago, the future of treating obesity and diabetes focused on end organs known to be involved in energy balance and glucose regulation, including the brain, muscle, adipose tissue, and pancreas. Today, the most effective therapies are focused around the gut. This includes surgical options, such as vertical sleeve gastrectomy and Roux-en-Y gastric bypass, that can produce sustained weight loss and diabetes remission but also extends to pharmacological treatments that simulate or amplify various signals that come from the gut. The purpose of this Review is to discuss the wealth of approaches currently under development that seek to further leverage the gut as a source of novel therapeutic opportunities with the hope that we can achieve the effects of surgical interventions with less invasive and more scalable solutions. While traditional approaches to treating obesity and type 2 diabetes have focused on end organs involved in energy metabolism, the gut has emerged as a source of our most effective therapies. From bariatric surgical procedures to pharmacological agents, harnessing the gut has and will continue to provide important therapeutic options for the treatment of these epidemic-level diseases.