Mast Cell-dependent Mesenteric Afferent Activation by Mucosal Supernatant From Different Bowel Segments of Guinea Pigs With Post-infectious Irritable Bowel Syndrome

Abstract

Background/Aims Mesenteric afferent nerves (MANs) play a pivotal role in the visceral-nociceptive perception. Inappropriate activation of MANs may be involved in the pathogenesis of post-infectious irritable bowel syndrome (PI-IBS). However, the underlying mechanisms remain unclear. We assessed the effects of mucosal mediators from different bowel segments of guinea pigs with PI-IBS on MAN firing and the role of mast cells. Methods PI-IBS was induced in guinea pigs by Trichinella spiralis infection. Inflammation in terminal ileum, proximal and distal colon was scored with hematoxylin-eosin staining, and mast cell infiltration was assessed with immunofluorescence. We determined the effects of supernatant extracted from the mucosa of different bowel segments of PI-IBS on MANs activity, and assessed the role of mast cells in this process. Results Eight weeks after infection, intestinal inflammation resolved, whereas mast cell numbers increased significantly in terminal ileum and proximal colon ( P < 0.05) compared with findings in controls. Mucosal supernatant from different bowel segments of PI-IBS models, but not from controls, significantly enhanced the frequency of MAN firing (terminal ileum 41.01 ± 7.60 Hz vs. 26.55 ± 0.67 Hz, P = 0.001; proximal colon 45.90 ± 11.20 Hz vs. 30.88 ± 6.92 Hz, P = 0.002; distal colon 48.25 ± 9.70 Hz vs. 29.47 ± 6.13 Hz, P < 0.001). In addition, the excitatory effects were inhibited by mast cell stabilizer Nasmil (terminal ileum, 32.71 ± 2.52 Hz, P = 0.030; proximal colon, 30.94 ± 4.44 Hz, P = 0.002; distal colon, 27.15 ± 5.83 Hz, P < 0.001). Conclusions Supernatant from the intestinal mucosa of different bowel segments of PI-IBS models markedly enhanced the MAN firing in a mast cell-dependent manner, indicating that mast cell-mediated MAN activation plays an important role in the pathogenesis of PI-IBS.

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

“…Additionally, the increase in contractions was mediated through activation of purinergic P2X receptors (cation‐permeable ligand‐gated ion channels that open in response to the binding of extracellular adenosine 5'‐triphosphate: ATP), prostanoid receptors, and capsaicin or vanilloid receptors 1 (TRPV1), but not serotonin, histamine, or tachykinin. Exaggerated physiological responses were observed when supernatants of mucosal biopsies were applied to in vitro cell‐systems, in tissues from laboratory animals or humans, or in vivo in animal models; many of these changes were attributable to mediators primarily originating from mast cells (histamine, tryptase, serotonin). All of these findings support the role of mast cell activation in the intestinal dysmotility that has been observed in IBS .…”

Mast Cells and Irritable Bowel Syndrome: From the Bench to the Bedside

“…11,13 The density of MCs in both the small and large bowel may be increased in patients with IBS, but the results are somewhat inconsistent. Some studies demonstrated the number of MCs or the area of mucosa occupied by MCs was increased in IBS patients, 5 moreover, it varies in different genders, 15 in distinct bowel segments 16 and in subgroups of IBS with higher MCs counts in diarrhea-predominant IBS (D-IBS) patients than constipationpredominant IBS (C-IBS) patients. 17,18 However, others suggested there was no significant change in MCs density in IBS.…”

Long-term Clinical Course of Post-infectious Irritable Bowel Syndrome After Shigellosis: A 10-year Follow-up Study

“…12,27 Additionally, functional gastrointestinal disorders following acute infectious gastroenteritis not only include PI-IBS, but also post-infectious dyspepsia. 18,28,29 The final symptom complex depends on the interaction between local mucosal injury and central factors including adverse life events, personality, and external stressors.…”