Signalling from the gut lumen

The lining of the gastrointestinal tract needs to be easily accessible to nutrients and, at the same time, defend against pathogens and chemical challenges. This lining is the largest and most vulnerable surface that faces the outside world. To manage the dual problems of effective nutrient conversion and defence, the gut lining has a sophisticated system for detection of individual chemical entities, pathogenic organisms and their products, and physico-chemical properties of its contents. Detection is through specific receptors that signal to the gut endocrine system, the nervous system, the immune system and local tissue defence systems. These effectors, in turn, modify digestive functions and contribute to tissue defence. Receptors for nutrients include taste receptors for sweet, bitter and savoury, free fatty acid receptors, peptide and phytochemical receptors, that are primarily located on enteroendocrine cells. Hormones released by enteroendocrine cells act locally, through the circulation and via the nervous system, to optimise digestion and mucosal health. Pathogen detection is both through antigen presentation to T-cells and through pattern-recognition receptors (PRRs). Activation of PRRs triggers local tissue defence, for example, by causing release of antimicrobials from Paneth cells. Toxic chemicals, including plant toxins, are sensed and then avoided, expelled or metabolised. It continues to be a major challenge to develop a comprehensive understanding of the integrated responses of the gastrointestinal tract to its luminal contents.