Gut feelings: the emerging biology of gut–brain communication

Abstract

Recent neurobiological insights into this gut–brain crosstalk have revealed a complex, bidirectional communication system that not only assures proper maintenance of gastrointestinal homeostasis and digestion but is likely to have multiple effects on affect, motivation and higher cognitive functions. Sympathetic and parasympathetic innervations modulate intestinal function and are likely to mediate the reported emotion-related patterns of regional changes in motor, secretory and possibly immune activity in the gastrointestinal tract. There are three basic mechanisms by which sensory information is encoded in the gut: by primary afferent neurons, by immune cells and by enteroendocrine cells. Both extrinsic and intrinsic primary afferents provide input to multiple reflex loops that are aimed at optimizing gut function and maintaining gastrointestinal homeostasis during internal perturbations. The output of enteroendocrine cells is involved both in the regulation of digestive functions through enteric nervous system circuits, as well as in the regulation of CNS processes through endocrine and paracrine signalling to vagal afferents. Immune cells in the gut remain immunologically hyporesponsive to commensal bacteria, while maintaining their responsiveness to pathogenic organisms, and their products indirectly influence the functional properties of enteroendocrine cells. Recent evidence suggests that various forms of subliminal interoceptive inputs from the gut, including those generated by intestinal microbes, may influence memory formation, emotional arousal and affective behaviours. The human insula, and related brain networks (including the anterior cingulate cortex, orbitofrontal cortex and amygdala), has emerged as the most plausible brain region to support this integration. It remains to be determined whether intuitive decision making is based on an interoceptive map of gut responses that enables the brain to make rapid gut-based decisions based on interoceptive memories of such responses. There is extensive evidence of alterations in brain–gut signalling systems during perturbation to gut homeostasis, in several chronic gastrointestinal disorders and in eating disorders. Further understanding of the bidirectional crosstalk between the brain and the digestive system may aid the development of effective therapies for these conditions.