Table.
The Known and Possible Mechanism of Inflammation in Patients With Overlap Syndrome of Irritable Bowel Syndrome and Functional Dyspepsia
| Pathogenic factors | Disease | Pathophysiological changes | Pathophysiological outcomes | Related symptoms |
|---|---|---|---|---|
| Gastrointestinal infection | IBS | Intestinal MCs, T lymphocytes ↑12,13 and inflammatory cytokines ↑19,20 | Increased intestinal permeability | Diarrhea33 |
| Downregulation and redistribution of ZO-1 and occludin33 | Visceral hypersensitivity | Abdominal pain | ||
| TRPV1, SP, and CGRP positive nerve fibers ↑38,39 | Colon transit and defecation ↑61,62 | |||
| Increased excitability of DRG and submucous plexus neurons54,55 | ||||
| Persistent activation of CRF neurons,59 CRF binding to CRF1 receptor61,62 | ||||
| FD | Gastric and duodenal MCs, eosinophils ↑14-16 | Damage of duodenal mucosal barrier | Epigastric burning16 | |
| Abdominal expression of ZO-1 and occludin36 | Visceral hypersensitivity | Early satiety18 | ||
| SP, CGRP positive nerve fibers ↑41,42 | Gastric contraction and gastric emptying ↓61,62 | |||
| CRF binding to CRF2 receptor61,62 | ||||
| SIBO | IBS | IL-1α and IL-1β ↑81 | Mild inflammation and immune activation of intestinal mucosa | Abdominal distention relieved by rifaximin83 |
| FD | NA | NA | Abdominal distention relieved by rifaximin84 | |
| Food allergy | IBS | Increased intervillous spaces and intraepithelial lymphocytes in intestinal mucosa87 | Increased intestinal permeability | |
| Titers of IgG antibody to specific food antigen ↑91 | ||||
| FD | Duodenal eosinophilia88 | NA | Early satiety88 | |
| Titers of IgG antibody to specific food antigen ↑92 | ||||
| Psychological or mental stress | CD4+ T lymphocytes ↓94 | Increased intestinal permeability | ||
| CRF secreted by hypothalamus ↑, degranulation of MCs and released TNF-α and tryptase ↑95 | Visceral hypersensitivity | |||
| Expression of occludin and ZO-1 in duodenal mucosal ↓94 |
SIBO, small intestinal bacterial overgrowth; IBS, irritable bowel syndrome; FD, functional dyspepsia; MC, mast cell; ZO, zonula occludens; TRPV1, transient receptor potential vanilloid type-1; SP, substance P; CGRP, calcitonin gene related peptide; DRG, dorsal root ganglion; CRF, corticotropin releasing factor; NA, not applicable.