Scattered throughout the epithelial lining of the gut wall are hormone-secreting cells, called enteroendocrine cells, which synthesise and secrete over 15 different hormones. Many of these gut hormones, including GLP-1, PYY and serotonin, have important metabolic roles. Enteroendocrine cells have changing receptor and hormone expression profiles along the length of the gastrointestinal tract, constantly move from the stem cell niche within crypts up to the intestinal villi, and have a high rate of turnover. This has made them difficult to study. Our recent research has demonstrated that enteroendocrine cells can sense and respond to their environment including nutrients , immune regulators  and clinically relevant drugs such as metformin . Their hormones act in a paracrine manner on other enteroendocrine cells and on nearby nerve endings, and in an endocrine manner to influence various metabolic pathways. The enteroendocrine cell density and function changes in metabolic disorders in humans including obesity  and gastroparesis , and we are the first to demonstrate in humans that signalling molecules associated with central control of body weight and metabolism, such as MC4R and α-MSH, exist within the human gut as functional systems . In addition, bi-directional signalling also occurs between the gut microbiome and enteroendocrine cells  and we have defined one such hormone as being central to the modulation of host metabolism by the gut microbiome . Such complex interactions between enteroendocrine cells and with the gut microbiome are likely of importance to type 2 diabetes and obesity.
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