Brain-gut axis: from basic understanding to treatment of IBS and related disorders

Abstract

The present review describes advances in understanding the mechanisms and provide an update of present and promising therapy directed at the gut or the brain in the treatment of irritable bowel syndrome (IBS). The diagnosis of IBS typically is based on identification of symptoms, such as the Rome III criteria for IBS in adults and children. The criteria are similar in children and adults. The focus of the present review is the bowel dysfunction associated with IBS.

Figure 1

Cortical modulation of homeostatic afferent input to the central nervous system. Prefrontal regions modulate activity in limbic and paralimbic regions, subregions of the anterior cingulate cortex, and hypothalamus, which in turn regulate activity of descending inhibitory and facilitatory descending pathways through the periaqueductal gray and pontomedullary nuclei. Activity in these corticolimbic pontine networks mediates the effect of cognitions and emotions on the perception of homeostatic feelings, including visceral pain and discomfort. Reproduced from ref. , Mayer and Tillisch. Annu Rev Med 2011;62:381–96.

Figure 2

Cl− transport in intestinal epithelial cells. At the basolateral membrane, Cl− enters the cell from blood across the Na+-K+-2Cl cotransporter. Na is expelled by the Na pump, and K leaves via a K channel. Na is shown crossing the cell layer via a paracellular pathway, but Na channels also exist (not shown). Both cystic fibrosis transmembrane regulator (CFTR) and ClC-2 Cl− channels are present on the apical membrane and can allow Cl− to exit the cell. Reproduced from ref. , Cuppoletti J, Malinowska DH, Tewari KP, et al. SPI-0211 activates T84 cell chloride transport and recombinant human ClC-2 chloride currents. Am J Physiol 2004;287:C1173–83.