From cytokines to toll-like receptors and beyond - current knowledge and future research needs in irritable bowel syndrome

Abstract

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.

Keywords: Immunity, Mucosal; Irritable bowel syndrome; Stress, psychological; Toll-like receptors.

Figure 1

Possible immunological responses in the gut mucosa related to developing bowel disorders. In healthy controls there is a tolerogenic reaction towards commensal microorganisms. However, it is possible that bacterial populations present in some patients or a genetic predisposition, may shift the response towards an immune activation in irritable bowel syndrome (IBS) or to a full-blown inflammatory response in inflammatory bowel disease (IBD).

Figure 2

Integrative model of irritable bowel syndrome (IBS) pathophysiology. IBS can develop from centrally dominant factors such as stress or luminal factors like dysbiosis triggering an altered immune response. Stress alters gastrointestinal motility mediated through the hypothalamicpituitary-adrenal (HPA) axis, and these motility abnormalities can modify the microbiota with the subsequent immune activation in the mucosa and stimulation of nerve terminals, generating symptoms of IBS. On the other hand, dysbiosis related to gastrointestinal infections, small intestine bacterial overgrowth or antibiotics may increase the epithelial permeability leading to contact between pathogens-associated molecular patterns (PAMPs) and toll-like receptors (TLRs) in the deeper layers of the gut with the subsequent host immunity response and IBS generation or symptom exacerbation. CRF, corticotrophin-releasing factor.