The blood-brain barrier as a regulator of the gut-brain axis

The gut-brain axis is involved in metabolic homeostasis through optimization of nutrient absorption and appetite regulation, and encompasses a two-way communication between the gastrointestinal tract and neural circuits in the brain. An important feature of this axis is the secretion of gut-derived peptide hormones which signal energy status to the brain, provoking adaptive behaviors such as food intake or satiation. However, the major integrator of gut signals, the arcuate nucleus of the hypothalamus, is protected by blood-brain barrier, an obstacle to free diffusion of circulating molecules. The aim of this chapter is to therefore review and summarize recent findings regarding the mechanisms underlying entry of gastrointestinal tract hormones into the central nervous system, and identify how these become dysregulated in socioeconomically-costly metabolic diseases such as obesity and type 2 diabetes.