Current insights into the innate immune system dysfunction in irritable bowel syndrome

Abstract

Irritable bowel syndrome (IBS) is a functional bowel disorder associated with abdominal pain and alterations in bowel habits. The presence of IBS greatly impairs patients’ quality of life and imposes a high economic burden on the community; thus, there is intense pressure to reveal its elusive pathogenesis. Many etiological mechanisms have been implicated, but the pathophysiology of the syndrome remains unclear. As a result, novel drug development has been slow and no pharmacological intervention is universally accepted. A growing evidence implicates the role of low-grade inflammation and innate immune system dysfunction, although contradictory results have frequently been presented. Mast cells (MC), eosinophils and other key immune cells together with their mediators seem to play an important role, at least in subgroups of IBS patients. Cytokine imbalance in the systematic circulation and in the intestinal mucosa may also characterize IBS presentation. Toll-like receptors and their emerging role in pathogen recognition have also been highlighted recently, as dysregulation has been reported to occur in patients with IBS. This review summarizes the current knowledge regarding the involvement of any immunological alteration in the development of IBS. There is substantial evidence to support innate immune system dysfunction in several IBS phenotypes, but additional studies are required to better clarify the underlying pathogenetic pathways. IBS heterogeneity could potentially be attributed to multiple causes that lead to different disease phenotypes, thus explaining the variability found between study results.

Mast cells are increased in the small intestinal mucosa of patients with irritable bowel syndrome: A systematic review and meta‐analysis

“…When analyzing data on mast cells in IBS, we should consider that these cells share many characteristics with eosinophils and basophils. The evidence for involvement of eosinophils and basophils in IBS is not as extensive as mast cells . Therefore, future studies should also consider evaluating the roles of eosinophils and basophils, as well as the cross talk among these immune cells in the pathophysiology of IBS.…”

“…The evidence for involvement of eosinophils and basophils in IBS is not as extensive as mast cells. 14,15,[61][62][63][64] Therefore, future studies should also consider evaluating the roles of eosinophils and basophils, as well as the cross talk among these immune cells in the pathophysiology of IBS.…”

Mucosal Microbiome Profiles Polygenic Irritable Bowel Syndrome in Mestizo Individuals

“…SNPs in the IL-6 region have been associated with an increased risk of developing PI-IBS. These SNPs were identified as independent risk factors for developing PI-IBS (Lazaridis, 2018).…”

Peroxiredoxin 1 as an inflammatory marker in diarrhea‐predominant and postinfectious irritable bowel syndrome

“…Although IBS is not as severe as bowel cancer, most patients with IBS must avoid diarrhea and abdominal pain through stress management and diet control, because these problems reduce their quality of life and considerably increase unemployment rates and medical costs. 13 This chronic, low-grade, subclinical inflammation is a continuation of IBS symptoms. 11,12 Innate immune system dysfunction and low-grade inflammation play important roles in the occurrence and progression of IBS.…”

“…11,12 Innate immune system dysfunction and low-grade inflammation play important roles in the occurrence and progression of IBS. 13 This chronic, low-grade, subclinical inflammation is a continuation of IBS symptoms. For example, T lymphocytes, B lymphocytes, mast cells, and cytokine concentrations are altered in the local colonic mucosa or systemic circulation of patients with IBS relative to healthy controls.…”