Activation of the mucosal immune system in irritable bowel syndrome
Open accessAbstract
Background & aims A role for the mucosal immune system in the pathogenesis of irritable bowel syndrome is suggested by its association with intestinal infections.Methods To investigate this, we performed histologic and immunohistologic studies on colonoscopic biopsy specimens from 77 patients with symptoms satisfying the Rome criteria and 28 asymptomatic control patients.Results Histologic assessment of biopsy specimens from symptomatic patients indicated 3 different groups. The first (38 of 77) had normal conventional histology; however, immunohistology showed increased intraepithelial lymphocytes (median, 1.8-fold; range, 1.74-1.86), lamina propria CD3(+) cells (2-fold; range, 1.55-2.91), and CD25(+) cells (6.5-fold; range, 4.98-8.13) compared with asymptomatic controls. The second group (31 of 77) had nonspecific microscopic inflammation and on immunohistology showed similar increases in lymphocyte populations (not significant vs. the uninflamed group) as well as increased numbers of neutrophil leukocytes and mast cells (P < 0.0001 vs. controls and the uninflamed group). The third group (8 of 77) fulfilled histologic and immunohistologic criteria for classic lymphocytic colitis.Conclusions Examination of colonoscopic biopsy specimens from patients meeting the Rome criteria for a clinical diagnosis of irritable bowel syndrome showed subgroups with normal and abnormal conventional histology. All groups showed increased numbers of activated immunocompetent cells in the intestinal mucosa on quantitative immunohistology, implicating the mucosal immune system in pathogenesis.
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Patients with IBS have increased concentrations of inflammatory/immune cells in intestinal tissue compared with controls.
“Evidence supporting this hypothesis includes increased concentrations of inflammatory/immune cells in intestinal tissue from IBS patients, altered levels of pro- and anti-inflammatory cytokines in the GI tract and peripheral blood of patients with IBS (Table 1) (11, 13, 24, 36, 46, 50, 51, 62, 73, 75, 89, 90, 94, 98, 102, 118, 121–124, 168, 174, 185, 187), and IBS-associated polymorphisms in genes”
From Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome (2013) · cites this paper as [36]
Concentrations of intestinal epithelial lymphocytes may be increased in the small intestine, colon, and rectum of patients with IBS or PI-IBS.
“The concentrations of intestinal epithelial lymphocytes (IELs) may be increased in the small intestine (73, 174, 185), colon, and rectum (36, 89) of patients with IBS or PI-IBS.”
From Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome (2013) · cites this paper as [36]
Patients with IBS have altered levels of pro- and anti-inflammatory cytokines in the GI tract and peripheral blood compared with controls.
“Evidence supporting this hypothesis includes increased concentrations of inflammatory/immune cells in intestinal tissue from IBS patients, altered levels of pro- and anti-inflammatory cytokines in the GI tract and peripheral blood of patients with IBS (Table 1) (11, 13, 24, 36, 46, 50, 51, 62, 73, 75, 89, 90, 94, 98, 102, 118, 121–124, 168, 174, 185, 187), and IBS-associated polymorphisms in genes”
From Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome (2013) · cites this paper as [36]
Increased concentrations of CD3+ T cells in the colon and rectum and in the myenteric plexus of the small intestine were increased in patients with IBS or PI-IBS compared with normal controls.
“Additionally, increased concentrations of CD3+ T cells in the colon and rectum and in the myenteric plexus of the small intestine were increased in these patients compared with normal controls (36, 46, 57, 58, 89, 94, 133, 168, 174).”
From Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome (2013) · cites this paper as [36]
There are no consistent differences in the tissue concentrations of activated mast cells in patients with different IBS subtypes.
“However, some studies failed to demonstrate increased activated mast cells in IBS patients (35, 36, 57, 58, 168) and there are no consistent differences in the tissue concentrations of activated mast cells in patients with different IBS subtypes (36, 189).”
From Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome (2013) · cites this paper as [36]
Some studies failed to demonstrate increased activated mast cells in IBS patients.
“However, some studies failed to demonstrate increased activated mast cells in IBS patients (35, 36, 57, 58, 168) and there are no consistent differences in the tissue concentrations of activated mast cells in patients with different IBS subtypes (36, 189).”
From Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome (2013) · cites this paper as [36]
Concentrations of cytotoxic CD8+ T cells may be elevated in the lamina propria of the colon of patients with IBS or PI-IBS, although this finding was disputed by others.
“Concentrations of cytotoxic CD8+ T cells, which comprise most of the intraepithelial T cell population (126) may also be elevated in the lamina propria of the colon of patients with IBS (46, 123) or PI-IBS (89) although this finding was disputed by others (36).”
From Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome (2013) · cites this paper as [36]
Patients with IBS may have increased numbers of activated T cells in the colon and peripheral blood compared with controls.
“In addition to elevated concentrations of T cells, patients with IBS may also have an increased numbers of activated T cells in the colon (36) and peripheral blood (122) compared with controls.”
From Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome (2013) · cites this paper as [36]
There is increasing evidence of activation of the intestinal immune system in IBS leading to micro-inflammation, with increased mucosal intraepithelial lymphocytes, mast cells and 5-hydroxytryptamine-secreting enterochromaffin cells.
“First, there is increasing evidence of an activation of the intestinal immune system in IBS leading in a micro-inflammation, with studies demonstrating increased concentrations of mucosal intraepithelial lymphocytes [65,66] , mast cells [6669] and 5hydroxytryptaminesecreting enterochromaffin cells [65] .”
From Gut microbiota role in irritable bowel syndrome: New therapeutic strategies (2016) · cites this paper as [66]
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References 21 · Cited by 833
Research works printed but not linked: 2
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- Authors
- Chadwick, V. S., Chen, W., Shu, D., Paulus, B., Bethwaite, P., Tie, A., & Wilson, I.
- Affiliations
- Calvary Wakefield Hospital (AU)
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2002-06
- Volume
- 122
- Issue
- 7
- Pages
- 1778-1783
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W2028889492
- Cited by
- 833
- References
- 21
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 11 · 2023: 35 · 2022: 19 · 2021: 18 · 2020: 23 · 2019: 21 · 2018: 25 · 2017: 30 · 2016: 44 · 2015: 39 · 2014: 52 · 2013: 43 · 2012: 60
- FWCI
- 26.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- NPARC (submittedVersion)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Medicine › Epidemiology › Microscopic Colitis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Keywords
- irritable bowel syndrome, mucosal immune system, intraepithelial lymphocytes, lamina propria lymphocytes, CD25+ cells, lymphocytic colitis, intestinal inflammation, mast cells, neutrophils, intestinal infection, pathogenesis
- MeSH terms
- Adult, Aged, Biopsy, Colon, Colonic Diseases, Functional, Colonoscopy, Female, Humans, Immune System, Immunologic Techniques, Intestinal Mucosa, Lymphocytes, Male, Middle Aged, Antigens, CD
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