The aetiology and pathology of IBS, a functional bowel disorder thought to lack an organic cause, is largely unknown. However, studies suggest that various features, such as altered composition of the gut microbiota, together with increased intestinal permeability, a changed balance in the enteroendocrine system and a dysregulated immune system in the gut, most likely have an important role in IBS. Exactly how these entities act together and give rise to symptoms is still unknown, but an altered gut microbiota composition could lead to dysregulation of the intestinal barrier as well as the enteroendocrine and the immune systems, which (through interactions with the nervous system) might generate symptoms. This Review highlights the crosstalk between the gut microbiota, the enteroendocrine system, the immune system and the role of intestinal permeability in patients with IBS.