Gut-brain communication: Role in energy and glucose metabolism Signaling between the gut and the brain involves a complex mix of nutrients, peptides, and microbes that could be targeted as therapies for obesity and diabetes. Our bodies regulate food intake and energy expenditure via cells in the intestinal wall that sense certain nutrients, then release peptides which activate neurons. A review by Frank Duca and graduate students Hallie Wachsmuth and Savanna Weninger at the University of Arizona, Tucson, USA, reveals a more complicated picture, with many different interacting neural and hormonal signals, with increasing evidence for the vital role played by the microbes in the gastrointestinal tract. In particular, the gut microbiome impacts food intake, fat formation, endogenous glucose production, and insulin sensitivity. Novel metabolic therapies could target specific signaling pathways between the microbes, gut, and brain. The gastrointestinal tract plays a role in the development and treatment of metabolic diseases. During a meal, the gut provides crucial information to the brain regarding incoming nutrients to allow proper maintenance of energy and glucose homeostasis. This gut-brain communication is regulated by various peptides or hormones that are secreted from the gut in response to nutrients; these signaling molecules can enter the circulation and act directly on the brain, or they can act indirectly via paracrine action on local vagal and spinal afferent neurons that innervate the gut. In addition, the enteric nervous system can act as a relay from the gut to the brain. The current review will outline the different gut-brain signaling mechanisms that contribute to metabolic homeostasis, highlighting the recent advances in understanding these complex hormonal and neural pathways. Furthermore, the impact of the gut microbiota on various components of the gut-brain axis that regulates energy and glucose homeostasis will be discussed. A better understanding of the gut-brain axis and its complex relationship with the gut microbiome is crucial for the development of successful pharmacological therapies to combat obesity and diabetes.
