The irritable bowel syndrome (IBS) is a complex disorder in which psychosocial, cultural and biological factors, interact. Recent knowledge in the pathophysiology of IBS, seem to combine issues such as a low grade inflammation or immune activation and dysbiosis that can trigger or exacerbate IBS. On the other hand, stress mediated through the hypothalamic-pituitary-adrenal axis can produce motility abnormalities that can modify the microbiota as well, with the subsequent immune activation in the mucosa and stimulation of nerve terminals, generating symptoms of IBS. Also, we speculate that, stress, dysbiosis or an underlying genetic predisposition, may increase the epithelial permeability leading to a contact between pathogens-associated molecular patterns and toll-like receptors in the deeper layers of the gut, developing a host immunity response and IBS generation. We believe that the role of toll-like receptors in IBS and elucidating the communication processes between the immune and the nervous system, warrant future research.